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1. eere 71 A 4 1 Structure of the schrodinger hosts File eee eeeeeseeeseeereeeees 71 A 4 2 Selection of the schrodinger hosts File esses 73 A 4 3 Testing the schrodinger hosts File ees 73 Appendix B Command Line Job Control 75 Bl Introduction iie pai elogio dde 75 B 2 Jobcontrol Syntax and Supported Commands 75 B 3 Using jobcontrol to Purge the Job Database sess 76 B 4 Detault Behaviots 2 6 tdem e ee hr ntes 76 B 5 Remote Job Submission ss TI B 6 The Job Control Scratch Directory eee TI B 7 The Job Record eei tmd eee eee 78 Appendix C Sample Output Files se 81 C 1 Sample Regression Output and Commentary esses 81 C 2 Trend Vector Output aient 85 C 3 Sample myfits File eee eee 88 CA QikSim Output 52 5 dome iae Ha tait dies 90 Appendix D Sample Input Files sense 93 Di Sample mol File eee 93 D 2 Sample Maestro formatted File 95 LIO E 99 QikProp 2 0 User Manual Chapter 1 User Manual Overview 1 1 Purpose This manual contains an introduction to the Maestro graphical user interface GUI and in depth instruction on using the QikProp adsorption distribution metabolism and excretion ADME prediction software program For information about features
2. W Replace Workspace start 1 E Import All Structures Use Graphical Info fatat 1 Include In Workspace First Imported Structure File hone 1 aurie tutorial Import import Fron Hide Help Figure 5 2 The Import panel 2 Click Import From to bring up the Import Structure Files file selector 3 Select lt working_directory gt ligs mae 4 Click Open 5 Choose Show Table from the Project menu in the Main Application Window The Project Table panel is displayed The contents of the ligs mae file are listed and each of the 200 entries are selected 22 QikProp 2 0 User Manual Unix Chapter 5 QuickTopics E Project Table table Scratch Project EI Table Select Selection Total Entries 200 Subset Entries 200 Selected Entries 200 Entries Properties AM a E mo1_0004 K mol 0004 nol 0007 LI nol_0007 nol_0008 Im nol_0008 Synchronize Yorkspace Changes J Mark Selected Entries Hide Help Figure 5 3 The Project Table panel with all entries selected In the next few exercises you will use QikProp to make predictions for this set of structures OikProp 2 0 User Manual Unix 23 Chapter 5 QuickTopics Using QikProp to Generate a Training Set In this exercise you will run QikProp in normal processing mode to create an input training file for a QikFit job which will be run in a later exercise 1 In
3. Descriptor Parameter Significance Partial F Partial R 2 stars 0 000000 0 0000 0 0000 0 0000 amine 0 000000 0 0000 0 0000 0 0000 QikProp 2 0 User Manual Unix 31 Chapter 5 QuickTopics OPpolrz 0 052912 0 0290 6 1028 0 0299 QPlogPC16 0 182341 0 0267 2 5284 0 0126 New Predictions N Calc Activity Compound 1 1 050474 mol_7147 The first section shown displays the molecule number experimental property value and property value calculated by the regression equations for each struc ture The Delta column shows the difference between the experimental and cal culated values and the Compound column gives the molecule name for each structure The next section shown gives along with the significance the parameter or coeffi cient calculated for each property The partial F and partial R are reported for each property Properties that were eliminated from the regression are assigned values of 0 000000 for all fields The last section New Predictions reports the calculated value for the test struc ture mol 7147 For a more detailed explanation of the QikFit out file refer to section C 1 Sam ple Regression Output and Commentary on page 81 32 QikProp 2 0 User Manual Unix Chapter 5 QuickTopics Predicting New Properties with the QPmyfits File While QikFit can predict new properties for a molecule in a test file during a run it is likely that you will want to use the subsequent lt jobname gt myfits
4. 5 In subsequent exercises you will run QikProp in normal mode so you must edit the QPlimits file again Open the OPlimits file with a text editor and replace the word fast after the Mode line with the origi nal text It does not matter what text replaces fast Save the change and close the file 6 Close the current project by selecting Close Project from Maestro s Project menu 28 QikProp 2 0 User Manual Unix Chapter 5 QuickTopics Creating a Training File for use with QikFit To investigate how to use the QikFit program you must first generate a training file During this exercise you will use the Microsoft Excel spreadsheet program to create the file Ordinarily when creating training files for use with QikFit you would add a column of new experimental data For use with this exercise a list of data has been provided in the tutorial directory Using the instructions in this exercise copy the list into the CSV file In the next exercise you will then use QikFit to fit to this data These instructions are specific to Excel but another comparable spreadsheet pro gram can be used 1 2 3 Launch Excel and from the File menu select Open From the Files of Type option menu select Text Files Navigate to the directory containing your ligands CSV file and dou ble click on the file name Note If file extensions are not visible on your computer ligands CSV is visible simply as ligands Open the file data
5. Stars Amines Nitro Acid Amides Rotor Reactv FGs CNS Actvty MW Dipole SASA FOSA FISA PISA WPSA Volume HB Donor HB Accptr Dip 2 V ADOSA Globularty Polariz delG C16 delG octnl Weight 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 ho HN NN OF pou ss A UU Us 00 QikProp 2 0 User Manual Unix Appendix C Sample Output Files delG water 1 00 log P o w 4 00 log S 1 00 PCaco BI 1 00 PCaco Affy 1 00 log BB 1 00 PMDCK Affy 1 00 log Kp 0 00 IP eV 0 00 EA eV 0 00 Metabolic 0 00 Number of Molecules 555 Euclidean Distance Tanimoto Coefficient N R 2 Name N TC Name 392 0 000 efavirenz Sustiva 392 1 000 efavirenz Sustiva 393 0 421 DPC961 393 0 995 DPC961 394 0 443 DPC963 394 0 993 DPC963 292 1 272 diuron 284 0 964 Diazepam Valium 383 1 306 neburon 295 0 958 DuPont697 401 1 631 thiocarcoxanilideUC781 373 0 950 midazolam 454 1 673 ralitoline93738 40 0 344 0 950 lansoprazole 379 1 780 nabumetone 401 0 932 thiocarcoxanilideuc781 552 1 961 chlorpyriphos 292 0 924 diuron 221 2 009 aminopyrine 356 0 917 loratidine 284 2 015 Diazepam Valium 402 0 917 pyridinoneL697661 386 2 030 2 methoxy nevirapine 1 552 0 917 chlorpyriphos 430 2 030 Phenacetin 457 0 907 riluzole1744 22 5 402 2 032 pyridinoneL697661 304 0 904 etoricoxib 302 2 068 estrone 397 0 903 4 methylMBI 309 2 076 fenfluramine 387 0 898 N
6. 0 2 8761 0 7590 1 4548 O 0 0 0 0 0 0 2 9299 3 2485 0 0642 N 0 0 0 0 0 0 2 5953 3 2856 2 1346 H 0 0 0 0 0 0 1 1702 3 5863 1 1852 H 0 0 0 0 0 0 2 6389 4 0760 0 9518 C 0 0 0 0 0 0 4 1456 2 6586 0 1451 N 0 0 0 0 0 0 3 6559 4 0183 1 7909 N 0 0 0 0 0 0 1 7482 4 6777 1 0746 H 0 0 0 0 0 0 4 5671 3 1780 1 3140 C 0 0 0 0 0 0 5 5067 2 9437 1 8006 H 0 0 0 0 0 0 1 4068 1 3086 3 9040 C 0 0 0 0 0 0 0 5953 1 1075 2 5358 C 0 0 0 0 0 0 0 6234 1 1467 5 0625 C 0 0 0 0 0 0 2 7342 1 5333 4 0568 F 0 0 0 0 0 0 0 7638 0 9553 4 9621 C 0 0 0 0 0 0 1 0923 1 1705 6 0343 H 0 0 0 0 0 0 1 3736 0 9416 3 6974 C 0 0 0 0 0 0 5125 0 7994 6 0795 F 0 0000 0 2 4417 0 7958 3 6192 H 0 0 0 0 0 0 1 1061 1 0878 1 5846 H 0 0 0 0 0 0 3 5305 1 2501 0 9434 H 0 0 0 0 0 0 0 9123 1 4674 0 5516 C 0 0000 0 0 7999 0 6477 0 5941 N 0 0 0 0 0 0 0 0604 2 4494 0 3148 N 0 0 0 0 0 0 1 8446 1 5419 1 0958 H 0o 0 0 0 0 QikProp 2 0 User Manual Unix 93 Appendix D Sample Input Files 0 9669 1 9641 0 3727 C 0 0000 0 1 8156 2 5467 0 7067 H 0 0000 0 qi 22 0 0 0 1 3 0 0 0 1 4 0 0 0 1 5 0 0 0 2 6 0 0 0 25 7 0 0 0 2 8 0 0 0 3 29 0 0 0 3 30 0 0 0 6 9 0 0 0 6 10 0 0 0 6 11 1 0 0 0 7 18 2 0 00 7 19 0 0 0 8 28 0 0 0 9 12 0 0 0 9 13 0 000 1214 2 0 0 0 12 15 1 0 0 00 1316 2 0 0 0 14 16 0 0 0 16 17 0 0 0 18 20 0 0 0 18 21 QO O rO 1924 2 0 0 0 9 27 Os 20 00 20 22 2 0 0 0 20 23 0 0 0 22 24 0 0 0 22 25 0 0 0 24 26 0 0 0 29 3
7. 0 0 acid 0 0 amide 0 7265 rotor 0 0 ErctvFG 0 0 CNS 88 QikProp 2 0 User Manual Unix 0 0 MW 0 0 dipole 0 0 SASA 0 0 FOSA 0 0 FISA 0 0 PISA 0 0 WPSA 0 002753 volume 0 007269 donorHB 0 5117 accptHB 0 6552 dip 2 V 4 512 ACxDN 5 SA 67 42 glob 0 0 OPpolrz 0 0 OPlogPC16 0 0 OPlogPoct 0 0 QPlogPw 0 0 OPlogPo w 0 0 OPlogS 0 0 BIPCaco 0 0 AffyPCaco 0 0 QPlogBB 0 0 AffyPMDCK 0 0 QikProp 2 0 User Manual Unix Appendix C Sample Output Files 89 Appendix C Sample Output Files OPlogKp 0 0 IP eV oro C 4 QikSim Output A The sorted Euclidian distances and Tanimoto coefficients are listed in the file lt jobname gt simout following the input weights from the limits file A typical example follows DSR RR RR RR RR ck ck ck ckckck ckck CARR RR KH KH RR RR RR RR RAR RR RR RCA RR ck k k kk KAKKKKAKKAKAKKAKKKKK RCA RE RR RR RC KA RR RR ck ck ck ckck ck kck ck ck ck kck ck A kk ckckck ck ck ck ck kk k kk kk Similarity Diversity Analysis Ckckck ck ck ck ck ck k k kk Ckckck ck ck ck ck k k kk kk QikSim Ver Cckckckckckckck ck ckck ckck ck ck ckckckck ckck ck ck ck ckck ck KH KH KK KA KH ckckck AK KH ck A ck ckck ck kck ck ck ck kck KA KH k k kk 2002 Ckckck ck ck ck ck ck kc k kk Cckckckckckckck kckckckck ck ckck ckckck ck ck ckck ck KK KH KH KH kck ck ckck ckckck ckck ck ck ck ck ck ck kck ck ck ck ck ck ck k ck k k kk 90 Descriptor
8. 096070 052627 o00000000000000 l Eoi Lo o000000000 l O 072959 Do A OO 37 8410 2432 1977 6562 9064 35 30 1792 0 zd 9880 1742 to 1 9110 to 1 3877 QikProp 2 0 User Manual Unix AffyPCaco QPlogBB AffyPMDCK OPlogKp IP eV EA eV metabol Constant N Exptl Activity 1 0 218000 2 0 988000 3 0 385000 4 0 060000 5 0 047000 6 0 885000 7 0 351000 8 0 320000 9 0 328000 10 0 333000 11 0 650000 12 0 048000 13 0 090000 14 0 802000 15 0 077000 16 0 126000 17 0 094000 18 0 575000 19 0 090000 20 0 660000 21 0 665000 22 0 155000 23 0 450000 24 0 567000 25 0 310000 26 1 911000 27 0 972000 28 0 694000 29 0 248000 30 0 930000 045724 056059 062430 090000 000000 000000 067720 369492 00000000 Calculated 0 0 0 0 0 0 e 060070 174155 527218 246985 268094 980918 132868 413756 156298 424696 151212 022045 253660 454939 037306 168723 292191 385865 159282 393315 663545 002271 000358 692126 376020 387744 073706 045378 045336 773856 Appendix C Sample Output Files Delta 157930 186155 142218 186985 221094 095918 218132 0 093756 0 1 lt 0 0 070045 71702 091696 498788 163660 347061 114306 042723 198191 189135 249282 266625 001455 157271 449642 125126 066020 523256 101706 351378 293336 156144 Compou
9. 4 4 Launching Command Line QikProp In a terminal window enter the command SSCHRODINGER qikprop options lt input file replacing lt options gt with any desired options and replacing input file with the name of the structure file to be evaluated 16 QikProp 2 0 User Manual Unix Chapter 4 Launching the Programs If the file resides in a directory other than the current working directory specify the path as well as the file name For more information about command line Qik Prop and the valid options see Chapter 8 Command Line QikProp on page 51 4 5 Launching QikFit In a terminal window enter the command SSCHRODINGER qikfit lt options gt lt training_file gt replacing lt options gt with any desired options and replacing lt training_file gt with the name of the comma separated value CSV file to which you have added a new column of experimental activity data For more information about QikFit see Chapter 9 QikFit on page 55 4 6 Launching QikSim In a terminal window enter the command SSCHRODINGER qiksim lt options gt CSV file replacing lt options gt with any desired options and replacing CSV file with the name of the CSV file that you want to evaluate For more information on Qik Sim see Chapter 10 QikSim on page 61 4 7 Displaying Command Syntax The start up script of each of these QikProp programs prints a brief summary of the available options and
10. Unix Chapter 2 The QikProp Product Family 2 1 QikProp QikProp is a quick accurate easy to use adsorption distribution metabolism and excretion ADME prediction program designed by Professor William L Jor gensen Based on years of Jorgensen s research QikProp predicts physically sig nificant descriptors and pharmaceutically relevant properties for organic structures either individually or in batches In addition to predicting molecular properties QikProp provides ranges for com paring a particular molecule s properties with those of 95 of known drugs Qik Prop also flags 30 types of reactive functional groups that may cause false positives in high throughput screening HTS assays QikProp has two available processing modes By default QikProp runs in normal mode predicting 36 properties for as many as 10 000 molecules in an hour Alter natively QikProp can be run in fast processing mode which predicts 32 properties rather than the default 36 In fast mode QikProp is able to evaluate approximately 150 000 compounds per hour on a 1 GHz Pentium processor The OPlimits file must be edited to switch from normal to fast processing mode This file can also be edited to specify the range of values which cause a molecule to be flagged as dissimilar to other known drugs See section 6 4 Using the QPlimits File on page 43 for more details about the QPlimits file QikProp output can be used as input for the QikFit an
11. combination of entries For instance click ing on an entry while pressing the Control key toggles that entry s selection sta tus If an entry is already selected clicking on an additional entry while pressing Shift will cause all entries listed between the two to be selected as well However there are shortcuts for selecting some entry groups on the Select pull down menu and the Select panel Open the Select panel from the Select pull down menu on the Project Table panel Once you have selected project entries you can manipulate them using tools accessed from the Selection pull down menu Clicking the right mouse button while the pointer is positioned over the Project Table so long as there is at least one entry in the table displays the Selection menu at the mouse position You can use the mouse to perform operations besides selecting entries For instance clicking on the corner of the Project Table panel and dragging resizes the panel Clicking and dragging with the middle mouse button on the boundary of a row resizes that row Finally clicking on selected entries and dragging allows you to reposition the entry in the Project Table The entries are placed after the first unselected entry that precedes the entry on which the cursor is resting when you release the mouse button For example if you select entries 2 4 and 6 and release the mouse button on entry 3 these three entries are placed after entry 1 because entry 1 is the f
12. in the Workspace you do not need to change the Source Of Job Input setting 6 6 Selecting a Job Output Incorporation Scheme QikProp job output can be incorporated into the Project Table in several different ways Select the desired incorporation scheme by selecting the appropriate Incor porate Output Into Project By setting on the QikProp panel By default the option Replacing Existing Entries is selected This option causes Maestro to replace each processed entry with the QikProp output structure and all of the pre dicted properties associated with that structure Usually this amounts to the addi tion of 36 new columns in the Project Table and the import of 36 QikProp properties Generally the output structure does not differ from the structure used as input However if QikProp determines that a structure is missing hydrogens QikProp modifies the input structure and replaces it with the corrected structure When preparing QikProp calculations you can also choose the Appending New Entries option which leaves the original entries untouched and adds rows in the Project Table that contain property data for each of the processed structures Appended rows appear at the end of the Project Table The third option allows you to choose not to incorporate the data into the project at all If you select the Ignoring Output option the output files are written to the specified directory but the predicted properties do not appear in the Project Tabl
13. name or code in the first column followed by the molecular properties and descriptors The new experimental property should be placed in the last column of each line If you place it in a different column you must specify the column number as a command line argument Use a spreadsheet pro gram to add the data column The number of descriptors that can be used for regression analyses is limited to 250 For trend vector analyses 2000 descriptors are allowed QikProp 2 0 User Manual Unix 57 Chapter 9 OikFit e For an analysis of either type no more than 2500 molecules can be processed in the same file The length of each line is limited to 10 000 characters 9 4 The Test File You can specify the name of a test file as a command line argument when you run QikFit This test file should contain descriptors and properties for molecules that are different from but structurally similar to those in the training set If you spec ify a test file the optimized regression calculated for the training set is used to pre dict the new experimental property for the molecules in this file Format Restrictions for the Test File The test file must be in CSV format The test file must not have a column containing the new experimental property The test file must have the same number of descriptors and properties as the training file not including the new experimental property The descriptors and properties must be in th
14. on which the job is run JobUser The userid under which the job is run 78 QikProp 2 0 User Manual Unix Appendix B Command Line Job Control Host The machine from which job was launched User The userid under which job was launched Dir The startup and output directory on Host Status The current job status ExitStatus The reason the calculation stopped Command The command used to start up the actual calculation Env Environment variable settings for the job StatusTime The time at which Status was last updated StopTime The time at which the calculation stopped StartTime The time at which the calculation started running LaunchTime The time at which the job was submitted MonitorInterval The interval sec between monitoring updates 0 if off StructureMonitorFile The name of the monitoring file holding the molecular structure The name of the file holding the final molecular struc StructureOutputFile ture InputFiles Files copied from the output directory to the job direc tory at startup OutputFiles Files copied from the job directory to the output direc tory at exit Files copied from the job directory to the output direc tory during monitoring LogFiles Monitoring files that grow throughout the job QikProp 2 0 User Manual Unix 79 Appendix B Command Line Job Control 80 QikProp 2 0 User Manual Unix Appendix C Sample Output Files C 1 Sample Regressi
15. option ceeneene 57 QikProp command line 16 launching from Maestro 16 qikprop command helps un ee 68 input file types 52 qikprop command syntax 51 QikProp jobs incorporation of output 44 inp t TOR d e op ose tp EMG 43 MONO Tee 45 multiple molecule processing 52 LETT I T HR TREE ERE E 41 output files KS V anne 48 Mae ea un 47 OUR sein nat 48 Dee 48 WANNE ae 49 Ol MAS a 47 starti i ns en tetes 44 QikProp panel eds 24 ACCESSIN Eun naie 41 QikSim PU 62 launching use 17 OULD UL eios e trat ent riea 38 TUNNEL es poete eta cre Uo tutus 38 qiksim command Arguments sacanear 61 help forn als 68 SITE en 61 QPlimits file 3 26 43 OP IO SB B trs EMT eu 5 DPS RASA nee 5 OPIOSK pa une 5 OPlogPCI6 anna 5 OPO SP OW s siet ine 5 QPlogPoet a uu nein 5 QikProp 2 0 User Manual Unix Index QPIO SPW un nike 5 OPIOSS unse 2 QPmyfits files 33 OPPO en 5 R restrictions for input structures 52 TOME I docta ME EL aac 8 S SAS A 4 scatter plot Greating zes 36 SCHRODINGER setting 15 schrodinger hosts file 71 Sidebar aieo peg 13 Sort Project Table panel 27 structures IP DOR IDE oce te 22 restrictions ansehen 52 ROUAUIN De ine 11 translating u a hie 11 T technical support rs 68 test file generating 30 training file Great eeu a eo 20 excludi
16. the Sets panel which canbe 1 Sets Clicking on the Pick All Atoms used to define subsets of atoms Pick All atons button selects all Workspace atoms Figure 3 3 The Pick State menu on the Main Application Window Sidebar 3 4 1 Pick States Maestro pick states allow you to specify how a pick is interpreted A click on a single atom can represent either the selection of only that atom or the selection of the residue chain molecule or entry of which it is a member You change the pick state by clicking the radio button that corresponds to your choice in the Pick States area of the Sidebar 10 QikProp 2 0 User Manual Unix Chapter 3 The Maestro User Interface 3 4 2 Picking Mode Maestro panels are amodal more than one panel can be open at any given time A panel need not be closed for an action to be carried out You might find it conve nient to leave frequently used panels open In contrast to modal panels which carry out designated actions only upon closing actions occur immediately in amodal panels once an operation and atoms have been specified To make you aware of this difference in functionality there is no Close option on the panels pull down menu Instead there is a Hide button in the lower left corner of each panel Since more than one panel can be open at a time the picking focus the designa tion of the panel that is intended to receive the picked atoms must be moved from one pa
17. this cycle not a problem keep going The results for the first cycle of the analysis are now output using all 37 descriptors The CSV file contains 38 columns as listed above however col umn 1 contains the molecule name Standard statistical measures are output including the r correlation coefficient rms error and Fischer F statistic A good background reference is D G Kleinbaum L L Kupper K E Muller and A Nizam Applied Regression Analysis and Other Multivariable Meth ods Third Edition Duxbury Press Pacific Grove 1987 Regression Analysis Cycle 1 R Squared 0 1061 RMS Error 0 8173 Average Error 0 5789 Sum of Squares 132 2716 F Statistic 0 5377 Degrees of Freedom 36 No of Data Points 200 Average Activity 0 9447 Exptl Activ Range 2 8760 to 2 7062 Calcd Activ Range 0 1684 to 1 7288 Activity in Column 38 Signif Cutoff 0 0006 Descriptor Parameter Significance Partial F Partial R 2 stars 0 023571 0 0000 1 8153 0 0091 amine 0 129837 0 0001 0 0127 0 0001 nitro 0 000000 0 0000 0 0000 0 0000 acid 0 147614 0 0001 0 3471 0 0018 amide 0 116963 0 0000 1 7936 0 0090 rotor 0 039570 0 0005 0 3740 0 0019 rctvFG 0 219500 0 0001 0 9128 0 0046 CNS 0 000056 0 0000 0 0444 0 0002 MW 0 003055 0 0094 4 5926 0 0227 dipole 0 002754 0 0000 2 5645 0 0128 SASA 0 001786 0 0105 5 4411 0 0267 FOSA 0 000094 0 0000 2 9814 0 0148 FISA 0 000335 0 0000 0 1149 0 0006 PISA 0 000180 0 0001 0
18. training out QikProp 2 0 User Manual Unix 33 Chapter 5 QuickTopics Creating a Plot of Project Table Properties In the next few exercises you will use the plotting capabilities of the Project Table to examine data produced by QikProp in the previous exercise In this particular exercise you will plot data for a subset of Project Table entries In the next exer cise you will create a different type of plot 1 Inthe Project Table panel select a subset of entries to plot by click ing on entry 1 holding down the Shift key and then clicking on entry 20 Entries 1 through 20 should now be selected 2 Choose New Plot from the Selection menu The New Series dia log box is displayed 3 To visualize the range of solvent accessible surface areas SASAs in the selected set of entries you will plot SASA versus Entry Name In the New Series dialog box under Plot Name type SASA For the x axis property leave Entry Name selected in the X Property box For the y axis property choose sasa News UOO O Plot Name sasa Series Name series X Axis X X Property Selected In LE vis title Y Axis Y Y Property mol vt a dipole E fosa fisa 1 Frequency Plot Style Of Drawing Color black a Line Style Solid Marker Filled square Line Width 1 New Cancel Figure 5 9 The New Series dialog box 4 Click New The plot is displayed i
19. txt The Text Import Wizard is displayed Click Finish It is not necessary to specify a delimiter because the file con tains only a single column of data A column of data named exp data is displayed This is our experimental property Copy the column of data and paste it into the first empty column in ligands CSV just to the right of the column that contains data for QPlogKhsa Save the file as training CSV by selecting Save As from the File menu and entering training CSV in the text box Ensure that CSV is selected from the Save as type option menu Click Save and close Excel QikProp 2 0 User Manual Unix 29 Chapter 5 QuickTopics Using QikProp to Generate a Test File QikFit can calculate the experimental property for molecules in a test file whose name is specified on the command line At the same time it can produce a file containing regression coefficients for the experimental value In this exercise you will use QikProp to generate the lt jobname gt CSV file for a molecule called mol 7147 for which there is no exp data value Instead of running QikProp through the Maestro interface you will submit the job from the command line Generally the command line option is intended for running jobs that consist of large numbers of structures To create a test file for use with QikFit enter the fol lowing command in a terminal window SSCHRODINGER qikprop test mae When the job is complete the follo
20. window is composed of the Title bar the Auto Help window the Main MenuBar the Sidebar the Workspace the Command Input Area and the Top View window Menu title Title Bar Maestro version 5 0 014 Main MenuBar Maestro Project Edit Display Applications Macrofiodel Analysis Help Tile Entries Clear Workspace Pick to Delete Atoms Pick State 4 Atoss Q ronds gt kesidees chains forse v motecates Maestro PDE Hol2 gt SD S O Entries ave sets 3 E Replace Workspace stare 1 viewing o Fick ATI Atons E Inport All Structures 1 t f ranstorm E Use Graphical Info Vocal 1 Save view Restore View 2 d d ef 7 LA er Rotate xw Right Mouse Means Middle Mouse Means Include In Workspace First Imported Structure File hone laurie tutorial Inport Translate w a transform Hide Advanced Mid Right Mouse Means Zoon siw Fit Enhance 3D Hide panel button 1 1 Res 1 Chn 1 Mol 1 Fick to Spot Center Panel specifi Help button Workspace Command Input Area Top View Viewing volume indicators StatusBar Clipping plane Figure 3 1 The Maestro Main Application Window OikProp 2 0 User Manual Unix 7 Chapter 3 The Maestro User Interface The functions of the Main Application Window components are as follows e Workspace displays drawn or read in stru
21. with the project unless you explicitly incorporate it into the project How ever you can use a scratch entry as input for some computations QikProp 2 0 User Manual Unix 9 Chapter 3 The Maestro User Interface 3 3 Maestro Workflow Paradigm The Maestro interface uses a define operation then pick atoms or bonds work flow paradigm That is the action to be performed must be selected and set up before the atoms to be operated upon can be designated For example to change the color of all atoms in an on screen structure to the color green you first select the color from the Atom Coloring panel and then pick the atoms to be colored 3 4 Picking Atoms Once an operation has been specified and set up atoms must be selected The name for this process is picking Picking is accomplished by clicking on desired structural elements in a Workspace structure The way in which Maestro interprets each mouse click is dependent on the pick state and the picking mode Clicking Tile Entries arranges all Tile Entries included entries into a square grid Clear workspace Clicking Clear Workspace in the Workspace and updates MERE removes all atoms from the Pick to Delete Atoms molecular coordinates Workspace Pick State Atoms gt Bonds Pick states that are available for the currently selected action appear unshaded vy Residues Y Chains Y Molecules Clicking the Sets button opens gt Entries
22. 0 User Manual Unix 71 Appendix A Configuring Job Control Schrodinger hosts file name localhost schrodinger usr local schrodinger_72b name ahost user your_userid_on_ahost processors 1 tmpdir ser name big_host user your_userid_on_big_host processors 16 tmpdir big scr schrodinger software Schrodinger_mmod72 name another_host processors 2 tmpdir ser schrodinger software Schrodinger_mmod72 End of Schrodinger hosts file For each computer that will be used there should be an entry in the schrod inger hosts file specifying the name of the computer In the example above the name of the first computer is ahost Additional lines can be specified for each host There can also be a special host entry with the name localhost which represents the computer that the user is logged into regardless of what the com puter is called The user line specifies the userid that will be used to log in to the remote host If the userid is the same on the job startup computer as on the remote host the userid for that remote host does not need to be specified in the schrodinger hosts file The processors line indicates the maximum number of processors that a par allel or distributed job should use on that computer This defaults to 1 if it is not given 72 QikProp 2 0 User Manual Unix Appendix A Configuring Job Control The tmpdir line for a given host specifies the location used for t
23. 0088 0 0000 WPSA 0 001837 0 0002 0 2818 0 0014 volume 0 000473 0 0026 6 1115 0 0299 donorHB 0 049118 0 0001 0 2993 0 0015 accptHB 0 000908 0 0000 0 0001 0 0000 82 QikProp 2 0 User Manual Unix Appendix C Sample Output Files dip 2 V 2 582746 0 0004 3 7342 0 0185 ACxDN 5 SA 13 058270 0 0006 1 2437 0 0062 glob 0 082376 0 0000 3 2992 0 0164 OPpolrz 0 059584 0 0394 6 1028 0 0299 QPlogPC16 0 049495 0 0024 2 5284 0 0126 QPlogPoct 0 055253 0 0101 0 9059 0 0046 OPlogPw 0 002370 0 0000 0 1069 0 0005 OPlogPo w 0 138717 0 0011 4 2445 0 0210 OPlogS 0 053854 0 0005 5 3425 0 0264 BIPCaco 0 000005 0 0000 0 0001 0 0000 AffyPCaco 0 000036 0 0003 0 1774 0 0009 QPlogBB 0 019367 0 0000 0 5385 0 0027 AffyPMDCK 0 000002 0 0000 0 0014 0 0000 OPlogKp 0 144400 0 0041 0 2152 0 0011 IP eV 0 005411 0 0000 0 0010 0 0000 EA eV 0 160889 0 0003 1 7278 0 0087 metabol 0 025477 0 0001 0 2521 0 0013 OPlogKhsa 0 233016 0 0000 5 6344 0 0277 Constant 0 907894 0 0133 The next cycle is performed after removal of the descriptors with significance values below the cutoff 0 0006 Regression Analysis Cycle 2 R Squared 0 0776 RMS Error 0 8303 Average Error 0 5823 Sum of Squares 136 4921 F Statistic 1 7766 Degrees of Freedom 9 No of Data Points 200 Average Activity 0 9447 Exptl Activ Range 2 8760 to 2 7062 Calcd Activ Range 0 4789 to 1 6891 Activity in Column 38 Signif Cutoff 0 0006 Descriptor Parame
24. 1 2 0 0 0 29 32 O 00000 3033 2 0 0 0 31 33 000 33 34 000 M END gt MOLNAME MFCD00004144 fluconazole gt lt MDLNUMBER gt MFCD00004144 MFCD00004144 gt lt MOLCODE gt MFCD00004144 94 QikProp 2 0 User Manual Unix Appendix D Sample Input Files As shown in the example above the standard MDL SD mol file format is com prised by the elements below Check to ensure that your mol files are formatted as demonstrated Line 1 Molecule name QikProp retains the first 40 characters for printing Line 2 Information on the origin of the file ignored by QikProp Line 3 Blank Line 4 Atom and bond counts Atom entries x y z in ngstr ms atomic symbol Bond entries ignored by QikProp Any additional entries ignored by QikProp except as noted below The data group for each molecule in a file is followed by this delimiter Some additional entries to standard mol files are processed as follows If there is an entry called lt MOLNAME gt QikProp reads the following line for the molecule name that is output in all files If there is an entry called lt MDLNUMBER gt or lt MOLCODE gt this entry is output after the molecule name in the lt jobname gt pro pout file D 2 Sample Maestro formatted File Below is the structural information for Diflucan the same molecule whose mol file was shown in section D 1 Sample mol File on page 93 The difference is that this is a Maestr
25. 5 to set the SCHRODINGER environment variable to point to the directory in which Maestro and QikProp are installed and then to launch Maestro QikProp 2 0 User Manual Unix 19 Chapter 5 QuickTopics Specifying a Maestro Working Directory When you use Maestro to launch QikProp jobs Maestro writes job output to the directory specified in the Directory folder of the Preferences panel By default the file i o directory the directory to which Maestro will write files is the direc tory from which you launched the Maestro program If you want output files to be placed in another directory you can change the preferences as described below 1 Open the Preferences panel from the Maestro menu in the Maestro Main Application Window 2 Click the Directory folder 3 Click the radio button corresponding to the directory you want files to be read from and written to E Delete Markers Font Size Proj ect Directory House File Suffi x Default directory for job startup and file i o 4 Maestro s current working directory gt Parent of project directory Project directory Project jobs directory Other specify below Directory currentdir Figure 5 1 The Directory folder of the Preferences panel 20 QikProp 2 0 User Manual Unix Chapter 5 QuickTopics Creating a Working Tutorial Directory In the SCHRODINGER qikprop v lt version gt tutorial directory of your Qik Prop distribution
26. 500 0 2 734200 1 533300 4 056800 0 0 763800 0 955300 4 962100 0 1 092300 1 170500 6 034300 0 1 373600 0 941600 3 697400 0 1 511500 0 799400 6 079500 0 2 441700 0 795800 3 619200 0 1 106100 1 087800 1 584600 0 3 530500 1 250100 0 943400 0 0 912300 1 467400 0 551600 0 0 799900 0 647700 0 594100 0 0 060400 2 449400 0 314800 0 1 844600 1 541900 1 095800 0 0 966900 1 964100 0 372700 0 1 815600 2 546700 0 706700 0 m bond 72 w ba P4 P4 bd bq DA Dd Dd Dd bd P4 P4 DS P4 P4 pd Dd Dd Dd bd DX DS P4 PX Dd PX Dd P Dd DS P4 p POR First column is bond index i m from a RH S90000000000000000000000000000000 RH H D D IND O0 N DO N IO D IO iS SO DO ND S ID N N NN amp D ND B 21 2 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 21 0 00000 0 00000 UNK 0590000909992 0792920905839 000 OO OO GC Oo 000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 SUNK SUNK SUNK SUNK SUNK SUNK SUNK SUNK SUNK SUNK SUNK SUNK SUNK SUNK SU
27. Application Window If Auto Help is available for the task you are per forming it will automatically be displayed there If the question you have concerns an interface element e g a button or option menu there may be Balloon Help for the item Position the mouse pointer over the element and pause in that position If there is Balloon Help for the element it appears within a few seconds in a gold text box If you have not found the help you need using either of the steps above click the Help button in the lower right corner of the panel for whose set tings you are seeking help The Help panel will be opened and a relevant help topic will be displayed If you are seeking help for a concept or action not associated with a panel you can access the Help panel from the Help pull down menu on the Main MenuBar You can also display the Help panel from the Main Application Window using the key combination Alt H See the Maestro User Manual OikProp 2 0 User Manual Unix 67 Chapter 12 Help 12 3 QikProp Help from the Command Line To get help for the qi kprop qikfit or qiksim commands type SSCHROD INGER lt command_name gt in a terminal window in which the SCHRODINGER environment variable has been set Replace lt command_name gt with the command for which you want help 12 4 Technical Support If you have questions contact Schr dinger using the information below Gener ally e mail correspondence is best because you can se
28. HRODINGER gikprop v lt version gt data myfits file 60 QikProp 2 0 User Manual Unix Chapter 10 QikSim 10 1 Introduction QikSim performs a similarity diversity analysis for a designated molecule in a QikProp lt jobname gt CSV file During the analysis QikSim compares the mole cule to all the other molecules in that lt jobname gt CSV file by first computing the Euclidean distance and the Tanimoto coefficient that relate the probe molecule to the others QikSim then sorts results from most similar to least similar Such anal yses are useful for deriving new leads from a given reference compound 10 2 Command Syntax To run QikSim enter the following command from a terminal window in which the SCHRODINGER environment variable has been set SSCHRODINGER qiksim lt options gt CSV file Here CSV file is the name of the file to be evaluated This file is a comma sep arated values CSV file containing the QikProp calculated properties of the mol ecules to be compared The optional QikSim command line arguments are described in the table below o out file The file in which the output of the QikSim analysis is writ ten The default is lt jobname gt out l limits file A file containing the range in which specified property val ues for each comparison molecule must lie By default the limits def file is used p molecule The row in the CSV file that contains the probe mole cule The defa
29. M Prediction of Drug Solubility from Monte Carlo Simulations Bioorg Med Chem Lett 2000 10 1155 1158 Jorgensen W L Duffy E M Prediction of Drug Solubility from Structure Ad vanced Drug Delivery Reviews 2002 in press Jorgensen W L Duffy E M et al Prediction of Cell Permeability from Simu lations To be published Jorgensen W L Prediction of Blood Brain Barrier Penetration and CNS Activity To be published Colmenarejo et al Cheminformatic Models To Predict Binding Affinities to Human Serum Albumin J Med Chem 2001 44 4370 4378 11 2 QikFit Multiple Linear Regression Kleinbaum D G Kupper L L Muller K E Nizam A Applied Regression Analysis and Other Multivariable Methods Third Edition Duxbury Press Pacific Grove 1987 Trend Vector Carhart R E Smith D H Venkataraghavan R J Chem Inf Comput Sci 1985 25 64 73 QikProp 2 0 User Manual Unix 65 Chapter 11 Bibliography 66 QikProp 2 0 User Manual Unix Chapter 12 Help 12 1 Getting Help on Program Installation For help with installing Maestro QikProp QikFit and QikSim see the Schr dinger Product Installation Guide included with your shipment 12 2 Getting Help from within Maestro The Maestro help facility consists of Balloon Help Auto Help and online help To get help on operating Maestro follow the steps below Check the Auto Help window located below the title bar of the Main
30. NK SUNK SUNK SUNK SUNK SUNK SUNK SUNK SUNK UNK SUNK SUNK SUNK SUNK UNK SUNK SUNK SUNK SUNK Ey Ey w Ey Ey Ey Ey CY iQ OY CY Oy I2 0 IP Narr I Q0 OY OY soa an 200000000000000000000000000000000 QikProp 2 0 User Manual Unix Appendix D Sample Input Files i_m_order i_m_to 29 30 10 11 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 28 12 13 20 21 24 38 39 40 41 42 43 44 97 QikProp 2 0 User Manual Unix Appendix D Sample Input Files 45 46 47 48 49 50 51 52 53 54 55 56 51 58 59 60 61 62 63 64 65 66 67 68 69 70 qd 72 19 20 20 20 21 22 22 22 23 24 24 24 25 26 27 28 29 29 29 30 30 31 31 32 33 33 33 34 27 18 22 23 18 20 24 25 20 19 22 26 22 24 19 31 32 33 29 33 29 30 31 34 33 The name of each field is listed near the top of the file then the data is included in one row for each atom For example for the first atom listed the first number is the atom index the second is the atom type the next three give the cartesian coor dinates and so on Bond information follows the atom information in a similar format 98 QikProp 2 0 User Manual Unix Index Symbols HSLALS u ng CSV Tile sinite Tae tile i asg out Tie ie ere tes QpSa Tile ote warning
31. PDIR on the remote machine The location indicated by the environment variable TMPDIR on the remote machine Finally if no other specification for lt tmpdir gt is found the directory HOME schrodinger tmp is used Environment variables on the remote machine are cre ated by invoking the user s remote shell rsh or ssh in the normal manner In all cases lt tmpdir gt is created if it does not exist When the job is finished the scratch directory is automatically removed if the fol lowing conditions are met The job s output files were all successfully copied back to the startup direc tory The scratch directory didn t exist before the job started A 3 Preparing for Remote Job Submission To run remote or distributed jobs it must be possible to execute remote commands using the rsh command or the ssh command without specifying a password This typically requires that either 1 A hosts equiv file exists in the etc directory on each of the computers This file should contain a list of computers amongst which users can log in without giving their passwords provided that their userids are the same on each of the machines Creating a hosts equiv file usually requires root permission or 70 QikProp 2 0 User Manual Unix Appendix A Configuring Job Control ii A rhosts file exists in the user s home directory on each of the remote com puters The rhosts file should list the names of the computers a
32. QikProp 2 0 User Manual Unix QikProp 2 0 User Manual Unix Copyright 2002 Schr dinger L L C All rights reserved Schr dinger QikProp and Maestro are trademarks of Schr dinger L L C MacroModel is a registered trademark of Schr dinger L L C August 2002 RV2000201 Table of Contents Chapter 1 User Manual Overview ecsssssssssssnssensnnsensnnsensnnsensnssnssnnee 1 1 1 Purpose iine ette Ee E Re eee eres 1 T 2 Document Conventions ete ft lier lines 1 Chapter 2 The QikProp Product Family 3 2 I OIKPIOD iu Re ed t a e a rer RD 3 2 2 OUI tgp eed ere e EE ees 6 2 3 OIKS HIE eines ire e RE Eb Serb ie edat at es iore beu conto 6 Chapter 3 The Maestro User Interface ses 7 3 1 The Maestro Main Application Window eee 7 3 2 The Project Facility eo nte ei tu e RE 8 3 3 Maestro Workflow Paradigm esee 10 3 4 Picking ATOMS 2 nitentem be roo epe OP Eh ib e Epi uet 10 34 T Pick States iita hats aet t ete bd 10 3 4 2 Picking Mode eR ped BER 11 3 5 Mouse Eunetions me ent En ee teenage Heel 11 3 5 1 Specialized Mouse Functions in the Project Facility 12 3 6 Sidebar Controls nn ee Dal er ee IEEE ie 13 3 7 Maestro Command Scripts 14 Chapter 4 Launching the Programs u 0c00ss000ss000snennssnennonnenne 15 4 1 Introduction ntn ara RR a 15 4 2 Environment Variables cc
33. Stop Kill and Update buttons are active but you can only use the Kill button To terminate a QikProp job select the desired job in the database list and then click the Kill but ton QikProp 2 0 User Manual Unix 45 Chapter 6 Maestro QikProp 46 QikProp 2 0 User Manual Unix Chapter 7 QikProp Output 7 1 Output File Types For every completed QikProp job the files lt jobname gt out mae lt jobname gt CSV lt jobname gt mae lt jobname gt gpsa lt jobname gt out are created where lt jobname gt is the stem of the input file name For example a job with an input file named ligs mae produces output files named ligs out mae ligs mae and so on In addition to these five standard files a lt jobname gt warning file is written if QikProp has difficulty processing a structure 7 1 1 The lt jobname gt out mae File Upon completion of a job QikProp creates the lt jobname gt out mae file This is a Maestro formatted structure file that contains the QikProp properties generated for each structure as well as structural information Importing the lt jobname gt out mae file into any future Maestro session places each of the structures in the file along with the associated properties in a separate entry in the Project Table 7 1 2 The lt jobname gt mae File Before Maestro passes a QikProp job on to the Job Control Facility QikProp first writes a Maestro formatted lt jobname gt mae file containing s
34. The provided experimental results and the results computed from the final regression equation are then listed for each molecule and the final value for each QikProp parameter is listed The values of parameters found not to have a significant linear relationship with the new experimental property are listed as 0 00000 84 QikProp 2 0 User Manual Unix Appendix C Sample Output Files N Exptl Activity Calculated Delta Compound 1 1 331762 1 206324 0 125437 mol_0004 2 1 217879 1 142674 0 075205 mol_0007 sseto 195 1 701800 1 127796 0 574004 mol 3013 196 0 590873 0 914083 0 323211 mol 3043 197 1 545472 1 169439 0 376033 mol 3066 198 0 332011 1 272036 0 940025 mol 3067 199 0 856038 1 145599 0 289561 mol 3085 200 1 838763 1 177887 0 660876 mol 3138 myfits file not written need 37 descriptors The program notes that the QikProp myfits file has not been written in this case because the input CSV file did not contain all 37 QikProp descriptors and properties This may be unintuitive at first because there are 38 columns of data listed at the top of the file Recall however that the first column con tains the molecule name Also for this particular run QikFit was told to fit to the last column of data QPlogKhsa As a result QikFit counts that column as experimental data and not as a QikProp descriptor so to QikFit it appears that one of the necessary descriptors is missing In an actual QikFit run you would a
35. User Manual Unix Chapter 7 QikProp Output QikProp makes entries in the lt jobname gt CSV file for any molecules with fatal errors Check the file for these messages after multiple structure runs See 7 1 6 The lt jobname gt warning File on page 49 for more information about warnings 7 1 6 The lt jobname gt warning File Warnings about potential problems with the input structures are written to the lt jobname gt warning file For instance warnings are issued when QikProp encounters empty input files ionic input structures structures with multiple frag ments and structures with missing hydrogens In addition to statements placed in the lt jobname gt warning file if multiple struc tures are being processed in a single run any structures with fatal errors e g dis allowed atom types are normally skipped over and entries are made in the lt jobname gt CSV file stating that the processing of the molecules failed After exe cuting QikProp for multiple structures you should a display the contents of the lt jobname gt warning file if present and b search for any occurrences of empty or failed in the lt jobname gt CSV file If QikProp encounters no problems with the processed structure s a lt jobname gt warning file is not generated 7 2 Output File Directory QikProp places any generated output files in the file i o directory specified in the Directory folder of Maestro s Preferences panel E Prefe
36. aestro copy the logged commands from the Command History list into the Script area of the panel and then save the list of copied commands iz Command Script Editor script a zl Conmand History The Command History window s 1 hidenanel ren displays a log Select All Deselect 411 ShowHide 1 Determine which of all com Copy Selection To Script Step Capy commands are mands that are W Log Commands logged in the issued inter Script Command History nally within MM E list using the Maestro when entryselect entry entry 2 1 4 hidepane table Show Hide Com showpanel rep you interact showpanel script mand panel with a panel accessed by click menu or struc ing Show Hide ture Run Script Step Script Expand Command Aliases Open Local Open Global Save As il Hide JL Help Figure 3 5 The Command Script Editor panel To run an existing command script first open the Command Script Editor panel from the Edit pull down menu in the Maestro Main Application Window Then click Open Local and navigate to the directory containing the desired script Click the name of a script in the Files list and then click Open The command script is loaded into the Script window of the Command Script Editor panel To execute the script click Run Script 14 QikProp 2 0 User Manual Unix Chapter 4 Launching the Programs 4 1 Introduction QikProp QikFit an
37. appropriate command syntax if the script is executed with no input file specified For example typing SSCHRODINGER qikprop prints out a synopsis of QikProp options QikProp 2 0 User Manual Unix 17 Chapter 4 Launching the Programs 18 QikProp 2 0 User Manual Unix Chapter 5 Quick Topics 5 1 Introduction The Quick Topics chapter of this document is designed to assist you in rapidly becoming familiar with the functionality of QikProp 2 0 Once you have worked through these exercises you will have an understanding of the basic QikProp QikFit and QikSim features This chapter assumes that you have already installed the Schr dinger software or that you have access to an installation of the Schr dinger software If you do not have access to the software you must install it For installation instructions see the Schr dinger Product Installation Guide It is also assumed that you have set the SCHRODINGER environment variable according to the instructions in sec tion 4 2 Environment Variables on page 15 5 2 Getting Ready to Use QikProp from Maestro Before you can run QikProp from Maestro you must first launch a Maestro ses sion To do so use the instructions below QikFit and QikSim have not yet been interfaced with Maestro so it is not necessary to launch Maestro to use these mod ules of the QikProp program Launching Maestro Use the instructions in Chapter 4 Launching the Programs on page 1
38. are processing structures but are postponing structure viewing and analysis 8 2 Issuing the qikprop Command To use QikProp from the command line open a terminal window and set the SCHRODINGER environment variable if it has not been set already For more information see section 4 2 Environment Variables on page 15 To run QikProp enter the command SSCHRODINGER qikprop options input file replacing lt options gt with any desired command line options and replacing input file with the name including path if the file is not in your current work ing directory of the file to be evaluated See section 8 3 Input Files below for more information on acceptable input file types The QikProp command line options are described in the table below HOST host Run the job on the specified remote host LOCAL Use the current working directory rather than a temporary scratch directory for scratch files WAIT Do not return to the command prompt until the job finishes The default is to run the job in the background NICE Run the job at reduced priority HELP Print the acceptable command line arguments and exit QikProp 2 0 User Manual Unix 51 Chapter 8 Command Line OikProp QikProp jobs regardless of whether they are submitted from the Maestro GUI or from the command line are managed by the Schr dinger Job Control Facility All jobs whether started from the command line or from Maestro can be monit
39. are two Maestro formatted multi structure files that you will use in the following exercises Before you begin the tutorial you must create a direc tory in which to write the files that are produced during the exercises To create the directory open a terminal window and do the following 1 Use the ca command to move to a directory in which you have write permission Create a directory called tutorial by typing the command mkdir tutorial In the text that follows we refer to this directory as the working directory Set the SCHRODINGER environment variable to the installation directory Copy the files ligs mae test mae and data txt to your working direc tory by entering the following command at the prompt Replace lt ver sion gt with the version number of your particular QikProp release cp SSCHRODINGER qikprop v version tutorial QikProp 2 0 User Manual Unix 21 Chapter 5 QuickTopics 5 3 QuickTopic Exercises Importing Structures to Use as QikProp Input When running QikProp from Maestro you can use as input for a job either the structure s rendered in the Workspace or entries that are selected on the Project Table panel In this exercise you will import structures into Maestro to use as QikProp input 1 Choose Import Structures from the Project menu in the Main Application Window The Import panel is displayed TS A Import import Format E Maestro gt PDB Hol2 vy SD
40. ccesecnsesnssssnsensnnenssnnnnnnennennssennnnnnnnnn 15 4 3 Launching QikProp from Maestro eee 16 4 4 Launching Command Line QikProp eee 16 4 5 Launching OikFit Sarre dede edad qa duse 17 4 6 Launching QikSim unies 17 4 7 Displaying Command Syntax esee ene 17 QikProp 2 0 User Manual i Chapter 5 QuicKTopi nannten ne 19 5 1 Introduction a eee ERR Hei 19 5 2 Getting Ready to Use QikProp from Maestro eese 19 Launching M estto ecd rH weosedebets 19 Specifying a Maestro Working Directory seen 20 Creating a Working Tutorial Directory eese 21 3 3 Quick Topic Exercises sis srl ea etus eie 22 Importing Structures to Use as QikProp Input 22 Using QikProp to Generate a Training Set sees 24 Running QikProp in Fast Processing Mode sss 26 Sorting Project Table Entries eee 27 Creating a Training File for use with QikFit esses 29 Using QikProp to Generate a Test File eee 30 Running QikFit enne ar ran 31 Predicting New Properties with the QPmyfits File 33 Creating a Plot of Project Table Properties sess 34 Creating A Scatter Plot idee eet at ia i 36 Running QikSim and Examining Output Data 38 2 459 UML YS coe nee e do
41. ch directory how to prepare your account for remote job submissions and how to modify the schrod inger hosts file A 2 The Location of the Scratch Directory When a scratch directory is created automatically it is named lt tmpdir gt lt userid gt lt unique_dir_name gt The lt unique_dir_name gt is usually the job name but it could also have a sequence number appended to it in order to make the directory name unique There are a number of ways to specify the lt tmpdir gt directory The Job Control system uses the first specification found from the following list e The directory specified on the command line using the TMPDIR option For example to specify the scratch directory for QikProp SSCHRODINGER qikprop TMPDIR scr qp tmp lt input_file gt The directory specified by the environment variable SCHRODINGER_TMPDIR if this variable is set on the machine on which the job is started For example a csh or tcsh user might enter the commands setenv SCHRODINGER TMPDIR scr qp tmp QikProp 2 0 User Manual Unix 69 Appendix A Configuring Job Control SSCHRODINGER qikprop lt job_name gt e Ifthere isa tmpdir line for the host entry in the host database file that location is used for lt tmpdir gt For remote jobs the following are also considered if none of the above specifica tions is found The directory specified by the environment variable SCHRODINGER_TM
42. cid groups non conjugated amides Number of easily rotatable bonds except for CXYZ X Y Z H halogen groups 1 0 The Euclidian distance calculation uses the weights from the limits file The Tanimoto coefficient calculation does not use the values of the weights but descriptors are ignored if they have zero weight QikProp 2 0 User Manual Unix Chapter 10 OikSim The limits file can be specified on the QikSim command line If no file is explicitly given the program looks for a file called limits in the current directory If no such file exists the default limits file SCHRODINGER giksim v1 0 data limits def is used If you want to use a customized limits file you should copy the default file to your working directory and modify it to suit your purposes 3 The row number of the probe molecule in the CSV file and the number of results to report You must look at the CSV file to find the row number of the probe molecule Remember that molecule x is in row x 1 owing to the header in line 1 for instance molecule 392 is on line 393 of the CSV file The default row is the last row QikProp 2 0 User Manual Unix 63 Chapter 10 OikSim 64 QikProp 2 0 User Manual Unix Chapter 11 Bibliography 11 1 QikProp Duffy E M Jorgensen W L Prediction of Properties from Simulations Free Energies of Solvation in Hexadecane Octanol and Water J Am Chem Soc 2000 122 2878 2888 Jorgensen W L Duffy E
43. conds 2 View the contents of ligands simout An excerpt from this file is shown below Euclidean Distance Tanimoto Coefficient N R 2 Name N TE Name 10 0 000 mol_0073 10 1 000 mol_0073 130 0 091 mol 1191 130 0 997 mol 1191 24 0 198 mol 0159 18 0 985 mol 0132 18 0 514 mol 0132 24 0 983 mol 0159 11 0 744 mol 0075 11 0 963 mol 0075 The output file should show mol 0073 the tenth structure in the input file as the first structure for which the Euclidean distance and the Tanimoto coefficient are reported The Euclidean distance for this molecule should be 0 000 and the Tan 38 QikProp 2 0 User Manual Unix Chapter 5 QuickTopics imoto coefficient should be 1 000 because the molecule is being compared with itself The next closest molecule is mol_1191 according to both the Euclidean dis tance and the Tanimoto coefficient 5 4 Summary You have completed the Quick Topic exercises More information about each pro gram Maestro QikProp QikFit and QikSim can be found in the correspond ing chapters of this manual QikProp 2 0 User Manual Unix 39 Chapter 5 QuickTopics 40 QikProp 2 0 User Manual Unix Chapter 6 Maestro QikProp 6 1 Opening the QikProp Panel To open the QikProp panel from Maestro first launch Maestro according to the instructions in Chapter 4 Launching the Programs on page 15 Then select Qik Prop from the Applications menu The QikProp panel is displayed DDD QikProp a
44. ctory instead The LOCAL option is used for this purpose For example SSCHRODINGER qikprop LOCAL job name Not every application supports this option When it is supported it can be used for both local and remote jobs If you run a remote job with the LOCAL option it is important to make sure that the startup directory is accessible from the remote machine The location of the scratch directory is normally chosen automatically according to settings made in the schrodinger hosts file However there are a number of alternative ways to control where it will be created For more information see Appendix A 2 The Location of the Scratch Directory on page 69 B 7 The Job Record The SCHRODINGER jobcontrol utility can also be used to examine the data in a job s job record The show action lists the complete database record for one or more jobs To make sense of this output it is useful to know that the job record is just a list of fields one on each line each consisting of a field name and its value Many of these fields contain information that is only useful to the Job Con trol Facility but a number may also be useful to users Some of the latter include Field name Meaning Jobld The job s Jobld ParentJobId The Jobld of the parent job if this is a subjob Name The job name Program The program name Project The project name JobDir The directory in which the job is run JobHost The machine
45. ctures e Main Menubar provides panel access via pull down menus Sidebar contains structure manipulation and pick state selection tools Auto Help displays automatic context sensitive help Top View displays Workspace structures as viewed from above Command Input Area provides a way to execute command line opera tions from within the Maestro interface StatusBar displays the number of atoms entries residues chains and molecules currently displayed in the workspace 3 2 The Project Facility Central to Maestro is the concept of a project There is always a project open in Maestro If you do not specify a project when you start Maestro Maestro creates a scratch project You can work in a scratch project but you must save it in order to use it in future sessions A project is a collection of chemical structures Entries and their associated data These structures and their data are graphically represented in the Project Table which displays an ordered list of entries and any associated data You can open the Project Table panel by choosing Show Table from the Project menu Entries are represented by rows in the Project Table Each row contains the row number the name assigned to the structures represented by the entry the entry s Workspace inclusion state any title associated with the entry and a button to access the Surfaces panel if there are surfaces associated with the entry If there are no surfaces as
46. d QikSim modules The QikFit module performs linear regression analyses for experimentally determined molecular properties The resulting regression equations can then be integrated back into QikProp and used to predict the experimental property for additional structurally similar molecules QikSim performs similarity diversity analyses on lists of structures based on QikProp descriptors QikProp can be run either from the Maestro GUI or from the command line QikProp 2 0 User Manual Unix 3 Chapter 2 The OikProp Product Family For each successfully processed molecule QikProp produces the following descriptors and properties Those that are not predicted in fast mode are marked with a dagger 1 molecule name Molecule name taken from the title line in the input structure file If the title line is blank the input file name is used stars Number of property or descriptor values that fall outside the 95 range of similar values for known drugs Outlying descriptors and predicted properties are denoted with aster isks in the gpsa file A large number of stars suggests that a molecule is less drug like than molecules with few stars amine Number of non conjugated amine groups nitro Number of nitro groups acid Number of carboxylic acid groups amide Number of non conjugated amide groups rotor Number of non trivial not CX3 non hindered not alkene amide small ring rotatable bonds retvFG Number of reac
47. d QikSim can all be run from the command line QikProp can also be run from the Maestro GUI Using Maestro to run QikProp gives you the advantage of being able to build structures or import structures into Maestro use them as input for a QikProp job and then use Maestro s analysis tools and Schr dinger s other computational programs to further investigate lead com pounds Whether you run QikProp from the Maestro GUI or from the command line you must set the SCHRODINGER environment variable This chapter describes how to launch Maestro and open the QikProp panel and how to submit QikProp QikFit and QikSim calculations from the command line 4 2 Environment Variables Before you can run Maestro QikProp QikFit or QikSim you must first set the SCHRODINGER environment variable In a terminal window use the appropriate version of the following command to set the SCHRODINGER environment vari able to point to the directory in which Maestro and QikProp are installed csh setenv SCHRODINGER lt installation directory path gt bash or ksh export SCHRODINGER lt installation directory path gt To avoid setting the SCHRODINGER environment variable manually each time you launch Maestro QikProp QikFit and QikSim from a new terminal window you can add the appropriate version of the above command to your login shell script file cshrc or login for csh profile for ksh or profile or bashrc for bash Also fo
48. d jobs Running jobs cannot be purged You must be careful not to purge completed jobs whose output you still intend to incorporate back into a Maestro project B 4 Default Behaviors All jobs run in the background automatically they are disassociated from the ter minal session or application from which they were launched As a result the job continues to run even if you quit Maestro or the terminal session from which you launched the job For command line jobs the UNIX command prompt returns right away without waiting for the job to finish This behavior isn t always desir able especially if you want to run the job in a script in which some subsequent action can be taken only after the job finishes To accommodate use in a script the command line option WAIT can be used to prevent the command prompt from returning until after the job finishes For example 76 QikProp 2 0 User Manual Unix Appendix B Command Line Job Control SSCHRODINGER qikprop WAIT lt job_name gt Even with this option however the calculation is still placed in the background so pressing Ctrl C or Ctrl Z will not affect it Every job is assigned a unique Jobld consisting of the name of the machine on which the job was launched a sequence number and a hexadecimal timestamp e g mirabelle 0 a1b2c3d4 B 5 Remote Job Submission The Job Control Facility allows jobs to be run on a remote host When remote job submission is possible the na
49. dd your experimental property to the 37 QikProp descrip tors and properties so there would be a total of 39 columns New Predictions N Calc Activity Compound 1 1 050474 mol 7147 Finally predictions for any molecules in the test CSV file are then listed C 2 Trend Vector Output Below is sample output from a trend vector analysis Commentary is provided in boldface text The output from the trend vector analysis is similar to output from a regression however there is only one analysis cycle and all descriptors are used The following results are for the same data as above This data also appears in the file called out produced by the QikFit run QikProp 2 0 User Manual Unix 85 Appendix C Sample Output Files QikFit 2 0 Trend Vector Analysis R Squared RMS Error Average Error Sum of Squares F Statistic Degrees of Freedom No of Data Points Average Activity Exptl Activ Range Calcd Activ Range Activity in Column T Vector Length Descriptor stars amine nitro acid amide rotor rctvFG CNS MW dipole SASA FOSA FISA PISA WPSA volume donorHB accptHB dip 2 V ACxDN 5 SA glob OPpolrz QPlogPC16 QPlogPoct QPlogPw QPlogPo w QPlogs BIPCaco 86 Trend Vec 0 042381 000000 049569 000000 003993 022023 053940 079080 000000 086363 043515 084027 059661 054163 086733 077500 057854 000000 082756 075023 088957 078093 023344 035054 113389
50. dded in the lt job name gt CSV training file QikProp does not attempt to determine the identity of the data in the lt jobn name gt myfits file It is therefore necessary that the 36 default QikProp descriptors and properties appear in the lt jobname gt myfits file and that they appear in the same order in which QikProp generates them The lt jobname gt myfits file for each of 4 possible fits lists the 36 QikProp pre dicted descriptors properties and coefficients that relate these values to the new experimental property 9 8 Using QikFit Output To Predict New Properties You can use the coefficients file lt jobname gt myfits with QikProp to predict addi tional properties using the following procedure 1 Open the lt jobname gt myfits file in a text editor 2 Above the title for the first fit enter the number of fits you want Qik Prop to read from the file For instance if you have added data for only one new property enter 1 3 Below the title for each fit enter the name of the property you would like to predict This name appears when you print out the file and it also appears as the column heading in the lt jobname gt CSV file 4 Save the file as OPmyfits into the current working directory 5 Run QikProp See Predicting New Properties with the QPmyfits File on page 33 for an exam ple of how to predict properties See Appendix C Sample Output Files on page 81 for a sample portion of the SC
51. e For more information on output files see Chapter 7 QikProp Output on page 47 6 7 Starting a QikProp Job You can launch a QikProp job from Maestro by clicking the QikProp panel s Start button For more information on running QikProp from the command line see Chapter 8 Command Line QikProp on page 51 44 QikProp 2 0 User Manual Unix Chapter 6 Maestro OikProp 6 8 Monitoring the Job After you click the Start button of the QikProp panel the Monitor panel is dis played automatically and the contents of the lt jobname gt out file are displayed as the file is written Monitor monitor a mij Constant 4 186 2 Total 0 054 Total 2 073 200 molecules vere successfully processed 0 failed Jz Monitor Pause Stop Update betach Resume Ku Delete Clear this box show Jobs From Current Project Only to show al jobs ret B ligands mo incorporated home heather schrodinge E j Hide Help Figure 6 3 The Monitor panel The name of the job will be placed in the job database portion of the Monitor panel and the job will be automatically selected in the database By default the Show Jobs From Current Project Only option is selected To show all jobs run from your user name clear the check box When there are no jobs currently running only the Monitor and Delete buttons are active While a job is running the Detach Pause Resume
52. e The four quantities listed in the breakdown log Po w log S log BB and log PMDCK are computed as a linear combination of more basic molecular proper ties In the breakdown QikProp lists the descriptor values multiplied by their coefficients for each derived property which if added yields the value listed under Total which is the predicted property value Descriptor values that are above the maximum observed in the training set used to develop QikProp are marked with an angle bracket lt 7 1 5 The lt jobname gt CSV File The lt jobname gt CSV file is a comma separated value CSV file that lists the 36 QikProp descriptors and predicted properties on one comma separated line per molecule The Unix version of QikProp creates a lt jobname gt CSV file for each job As with the other output files the stem of the lt jobname gt CSV file corre sponds to the jobname entered in the Maestro QikProp panel The format of the lt jobname gt CSV file allows you to import it into spreadsheet programs such as Excel or analysis programs such as JMP You might want to do this to create a training file for use with QikFit See 9 3 The Training File on page 57 for more information about QikFit training files When QikProp writes this file it converts any commas appearing in molecule names to semicolons and it removes any blanks from molecule names The lt jobname gt CSV file can also be used as input for QikSim jobs 48 QikProp 2 0
53. e defaults 4 Scroll down to the end of the file Locate the line that begins with Mode Replace the text on the next line with the word fast Save the change and close the file 5 Ensure that all entries in the Project Table panel are selected then open the QikProp panel from the Applications menu in the Main Application Window 6 In the QikProp panel s Job text box type QPfast For Source of Job Input choose Selected Entries and under Incorporate Output Into Project By choose Appending New Entries 26 QikProp 2 0 User Manual Unix 7 Chapter 5 QuickTopics Click Start The job runs in a few seconds When it finishes the Project Table contains 400 entries Sorting Project Table Entries In this exercise you will use the Project Table panel s sorting function to help compare the results from fast mode to the results from normal mode 1 2 In the Project Table panel choose Select All from the Select menu Choose Sort from the Table menu The Sort Project Table panel is displayed Ensure that Ascending is selected for the Order option Choose Entry Name and click Sort selected table rows The row for each fast mode entry is now directly underneath the row for the corresponding normal mode entry vis title n stars n amine n nitro n acid Order Ascending Sort selected table rows Hide Help Figure 5 7 The Sort Project Table Panel Scroll through the Project Table and c
54. e same order as in the training file This order is the order in which they would appear if the file had been generated using QikProp It is possible to generate the test and training files with programs other than QikProp so long as the QikProp property order is preserved 9 5 Significance Cutoff Values For the regression analysis only descriptors with little effect on the fit are pruned in a series of up to 10 calculation cycles The significance is a measure of the quantitative effect of a change in the descriptor on the sum of squares error SSE Selecting higher values for the significance will cause more descriptors to be dis carded The default significance cutoff is 0 0006 If you want to change this value use the c option to specify an alternative value 58 QikProp 2 0 User Manual Unix Chapter 9 QikFit 9 6 Running on a Remote Host Before you can run a QikFit job on a remote host you must configure your Schr dinger Job Control facility by adding the host names that you want to use to the schrodinger hosts file For more information on Job Control configuration see Appendix A Configuring Job Control on page 69 After you have Job Control configured you can run QikFit jobs on a remote host by using the HOST option to specify the name of the desired host 9 7 Output Files QikFit results are written to the lt jobname gt out file If QikFit finds exactly 37 descriptors and properties 36 from QikProp and one expe
55. e the file SSCHROD INGER gikprop v lt version gt molfiles many mol Functional groups on input structures must be in their neutral state e g amines cannot be protonated and acids cannot be deprotonated 52 OikProp 2 0 User Manual Unix Chapter 8 Command Line OikProp QikProp makes adjustments for the proper protonation state in its pre dictions For mol and PDB files the allowed atom types are H C N O E Al Si P S Cl Br and I In fast processing mode all atom types are per mitted though some results might not be valid if atoms other than the above PM3 atoms are used QikProp 2 0 User Manual Unix 53 Chapter 8 Command Line OikProp 54 QikProp 2 0 User Manual Unix Chapter 9 QikFit 9 1 Introduction QikFit generates linear regression equations that describe the relationship between a new user added experimental property and applicable default QikProp descrip tors and properties Using the following equation QikFit performs iterative calcu lation cycles to obtain optimized coefficients for QikProp properties that correlate linearly with the new property P DK T Co In the above equation P is the property or activity that is to be predicted for mol ecule j the c values are the regression coefficients is the ith relevant property for molecule j and cg is a constant At the end of each calculation cycle QikFit discards properties that are not correlated with the new property by
56. e xy g EEE Click to open the Advanced Transforma Use these option menus to change the axes of rotation Right Mouse Means and translation Translate XY oo tion panel and define atom subsets for local Advanced translations and rotations Click to position the on Mid Right Mouse Means A screen molecule so that Use this option menu to it fits in its entirety in the Zoom Slow 3 T select a zooming speed Workspace i Ut Fit Enhance 3D 7 Click to move the clip ping planes to a position Enable this toggle button and click Pick to Spot Center which optimizes 3D cues on a Workspace atom to reposi tion the structure so that the selected atom is in the center of the Workspace Figure 3 4 Transformation controls on the Main Application Window Sidebar QikProp 2 0 User Manual Unix 13 Chapter 3 The Maestro User Interface 3 7 Maestro Command Scripts Although there is a provision for performing nearly all Maestro supported opera tions by interacting with menus and panels the operations can also be performed using Maestro commands or compilations of these commands called scripts Command scripts can be used to automate lengthy procedures or repetitive tasks And because all Maestro commands are logged and displayed on the Command Script Editor panel it is not necessary to memorize the commands for every oper ation Simply perform the desired operations once using the menus and panels within M
57. ed by Professor William L Jorgensen If you desire to use limits other than the default limits you can edit OPlimits In the QPlimits file beneath the name of each property are the current limits for that property These limits can be deleted and replaced by user specified minimum and maximum values Structures that have properties which do not lie within the limits will then be flagged with an asterisk in the output files To run in fast processing mode the word normal at the end of the QPlimits file should be replaced by the word fast An excerpt from QPlimits is shown below Molecular Weight standard is 130 0 725 0 130 0 725 0 Dipole Moment D standard is 10 47 1235 Qu 32 25 Total SASA standard is 300 0 1000 0 300 0 1000 0 Mode normal or fast normal 6 5 Specifying an Input Source When running QikProp jobs from the Maestro interface you can use Workspace structures or selected entries in the Project Table panel as input To evaluate structures from a file you must import the structures into a project using the Import panel select the desired structures in the Project Table all new structures are selected by default and enable the Selected Entries button located under Source of Job Input on the QikProp panel The default setting for QikProp job QikProp 2 0 User Manual Unix 43 Chapter 6 Maestro OikProp input is Workspace To perform QikProp evaluations for the structures currently appearing
58. emporary files on that host This directory should be local to the remote machine e g not NFS mounted it should have sufficient disk space available and the user should have write access The schrodinger entries are used to specify the location of the directory in which your Schr dinger software is installed on the remote machine This entry allows the user to select which of several versions of our software to use on the remote machine in case more than one version is installed The schrodinger entry is also useful if a user s default shell does not set the SCHRODINGER envi ronment variable on remote machines when using rsh or ssh A 4 2 Selection of the schrodinger hosts File The hosts database file used for a given job is the first one found in the following list 1 The file specified by the optional environment variable SCHRODINGER_HOSTS 2 The schrodingerhosts file in the current directory 3 The schrodinger hosts file in HOME schrodinger 4 The schrodinger hosts file in SSCHRODINGER A 4 3 Testing the schrodinger hosts File The schrodinger hosts file can be tested using the command SSCHRODINGER hunt rtest This command tests the first schrodinger hosts file found in the list above exclud ing the one specified by HOSTFILE This command also attempts to contact each of the hosts listed and thus also serves as a check on host accessibility and on whether remote login has been set up appropriately on the various host
59. file eee A accptHB una ente ACKDNA SISA nern ALLY PC LO iere A ffyPMDCK eee analyses trend vector atoms PICKING Auto Help B Balloon Help BIPCaCO ueneno eut C Command Input Area concatenated mol files D dP ZA V oer een ete essa ade dipole enm DISPLAY setting QikProp 2 0 User Manual Unix donorHB sense 5 E EA ENV Jaare te so siia 5 ntries in ee 8 exelimding vlt ae 9 Include Sera near 9 environment variables setting 15 F fast processing mode 26 file i o directory a 49 BIS A SR ge hades 4 FOSA sisina Ert IR 4 G loben 5 H host selection cnnn 41 42 I TPE intro gie 5 J jobcontrol utility purging database with 76 Syntax TOR se 75 jobs TeCOE eaa a aai 78 remote submission 70 77 scratch directory for 69 77 M Maestro Main Application Window 7 workflow paradigm 10 99 Index working directory specifying 20 Main Application Window 7 molecule name nn 4 Monitor panel ns 25 mouse functions 0 eeeeeeeeteeeeeeee 11 DANS ud Solar ee 4 N New Series dialog 34 O online helps rer 67 out mae file uide ciae Decet 47 P Pick Statemen
60. file to allow QikProp to begin predicting the new property along with the 36 default properties and descriptors for several molecules at once The training myfits file that was generated in the last exercise contains the coeffi cients necessary for QikProp to predict exp data for molecules that are structur ally similar to those molecules included in the file However in this exercise for cross reference purposes we will use training myfits with the same set of training molecules those from the file ligs mae that were evaluated in the previous exercises Follow the instructions below to use fraining myfits in a QikProp run 1 Rename the training myfits file OPmyfits and ensure that the OPmyfits file is in the current working directory 2 Import ligs mae into Maestro 3 Open the QikProp panel from the Applications menu Type ligands2 in the Job text box and under Incorporate Output Into Project By again choose Replacing Existing Entries 4 Click Start The Hydrogen Lone Pair Fixup panel is displayed Choose Fix For All This job produces the files ligands2 out mae ligands2 out ligands2 CSV and ligands2 gpsa This time an additional property appears in the Project Table under the heading myfit1 Look at this data and compare the predicted exp data val ues with the originals in training CSV Note that the predictions that appear in ligands2 CSV are the same as the calculated values reported for each structure in
61. ikProp 2 0 User Manual Unix 75 Appendix B Command Line Job Control The optional lt job selection gt consists of one or more Joblds job names status codes or queries It can also be the word all to select all the jobs in the jobs database The default selection is the query status completed A query takes the form lt field gt lt op gt lt value gt where field is one of the field names in the job record The most useful fields for queries are Name Program Host Dir JobHost JobDir Status and ExitStatus The op is either equals or is not equal to Use the wildcard character to match a single unspecified character or to match zero or more unspecified characters Examples of valid queries include program impact jobhost abigail exitstatus fin ished name tmp dir my project dir B 3 Using jobcontrol to Purge the Job Database Normally when running jobs from Maestro s Project Facility the database record for a job will be cleared once the job is incorporated back into a Maestro project Not all jobs are incorporable however for this and other reasons job records might not get deleted automatically and the jobdb directory might become full over time The SCHRODINGER jobcontrol utility can be used to purge the job database For example the following command purges the entire database SSCHRODINGER jobcontrol purge all This command only affects complete
62. ikprop Job ligands Login laurie Source Of Job Input gt Workspace Selected Entries Incorporate Output Into Project By gt Appending New Entries Replacing Existing Entries lt Ignoring Output Start Hide Help Figure 6 1 The QikProp panel To launch a job from the QikProp panel you must first specify a job name a host an input source and an incorporating mechanism If you wish to use fast process ing mode you must also edit the OPlimits file 6 2 Naming the QikProp Job By default when the QikProp panel is first opened the job name qikproptmp appears in the Job text box You can accept this default name and run a calcula tion but Maestro s Job Control Facility does not allow you to run multiple jobs with the same name To run a job that has the same name as a previous job you must first remove files associated with the first job 6 3 Selecting a Host Computer If you want to run QikProp locally you do not need to configure your system If you want to run a QikProp job on a remote computer you must do the following four steps QikProp 2 0 User Manual Unix 41 Chapter 6 Maestro OikProp Borm panel Restart Maestro Prepare the computers and accounts Create a schrodinger hosts file Select the desired host from the Hosts option menu on the QikProp The first three steps need to be performed only once after Maestro is installed unless more hosts are added The fourth s
63. ing a plot indicates that it is selected You can select plots by clicking the arrow icon in the tool bar and then clicking on the plot Once a plot is selected you can perform various operations on it To view only the new plot which is the only one currently selected choose Display Only Selected Plots from the Plot menu To view both plots again use the Plot menu to choose first Select All and then Display Selected Plots Both plots will then be part of the project and will be saved with the structural and property data In the subsequent exercise you will execute QikSim from the command line so you may now close Maestro QikProp 2 0 User Manual Unix 37 Chapter 5 QuickTopics Running QikSim and Examining Output Data QikSim ranks molecules based on structural similarities to a specified reference molecule As the basis for comparison QikSim uses the Euclidean distance and the Tanimoto coefficient To perform a QikSim calculation you must specify a reference or probe structure The first structure will be used by default but any structure in the file can be specified with the p option Use the following instruc tions to perform the QikSim calculation 1 Runa QikSim calculation by typing the following command in a ter minal window SSCHRODINGER qiksim p 10 ligands CSV The p option selects the tenth structure as the probe molecule All other structures are compared to structure ten The job should run in a few se
64. irst unselected entry that precedes entry 3 To move entries to the top of the table drag them above the top of the table to move entries to the end of the table drag them below the end of the table A summary of project based mouse functions is provided in the following table Task Mouse Operation in the Project Table Entry selection Left click Display of Selection menu Right click Multiple entry selection Shift click Toggles entry selection status Control click Move entry Click drag 12 QikProp 2 0 User Manual Unix Chapter 3 The Maestro User Interface 3 6 Sidebar Controls The Main Application Window Sidebar contains controls related to picking to saving and restoring the viewing transform and to molecular coordinate transfor mations translations and rotations To specify an axis other than the default value of xy for translations or rotations select the option corresponding to the desired axis from the Rotate or Translate option menu To specify whether you would like all atoms in the Workspace to be rotated or translated or just a subset enable the appropriate toggle button Global to move all atoms or Local to move only selected atoms These buttons appear on the Advanced Transformation panel which you open using the Advanced button on the Sidebar These buttons allow you to store a viewing transform and reverttoit at a later time Save view Restore View Middle Mouse Means Rotat
65. mand SSCHRODINGER qikfit lt options gt lt training file gt Here lt training file gt is the name including the path if the file is not in your cur rent working directory of the training file to be evaluated The training file is a comma separated value CSV file containing the QikProp calculated properties to be used in the regression and a column of activities to be fit See section 9 3 below for more information on training files The optional QikFit command line arguments are described in the table below For more information see the relevant sections later in this chapter a lt column gt The column containing the new property data in the training file A lt column gt of O selects the last column By default the last column is assumed to hold the new property data c cutoff Properties whose contribution to the fit are below the signifi cance cutoff are iteratively removed from the fit The default cutoff is 0 0006 o lt out file gt The file in which the output of the analysis is written The default is lt jobname gt out t test file An optional comma separated value CSV file containing the QikProp properties of molecules for which activity values will be predicted using the best fit coefficients x lt column gt A column to be excluded from the regression analysis By default all columns are always used Only one column to be excluded can be specified To exclude more than one column you mus
66. me This is the key term in the Kirkwood Onsager equation for the free energy of solvation of a dipole with volume V Index of cohesive interaction in solids This term represents the relationship accptHB JdonorHB SA see Bioorg Med Chem Lett 10 1155 2000 Globularity descriptor 4nr SASA where ris the radius of a sphere with a volume equal to the molecular volume Glob ularity is 1 0 for a spherical molecule Predicted polarizability in cubic ngstr ms Free energy of solvation in hexadecane Free energy of solvation in octanol Free energy of solvation in water Predicted octanol water partition coefficient Predicted aqueous solubility log S S in moles liter is the concentration of the solute in a saturated solution that is in equilibrium with the crystalline solid Predicted apparent Caco 2 cell permeability in nm sec using the Boehringer Ingelheim scale Predicted apparent Caco 2 cell permeability in nm sec using the Affymax scale Predicted brain blood partition coefficient Predicted apparent MDCK cell permeability in nm sec using the Affymax scale Predicted skin permeability PM3 calculated ionization potential PM3 calculated electron affinity The number of likely metabolic reactions Prediction of binding to human serum albumin QikProp 2 0 User Manual Unix 5 Chapter 2 The OikProp Product Family Additional information on many of these properties can be found in the directo
67. me of the remote machine is selected using a popup menu in the Maestro panel from which the job is launched The special host name localhost can always be used to launch a job on the current machine A MacroModel Impact or QikProp command line job can be submitted to a remote host by using the HOST option to specify the remote host name For instance SSCHRODINGER qikprop HOST host name job name Certain information about the remote machine is required to launch a remote job This information is taken from the schrodinger hosts file which is described in some detail in section A 4 The schrodinger hosts File on page 71 It may be necessary for you or your system administrator to edit this file in order to make remote jobs possible In particular the machines listed in Maestro s popup host selection menu are taken from the schrodinger hosts file B 6 The Job Control Scratch Directory Most jobs now run in a scratch directory by default rather than in the directory from which the job was started When a scratch directory is used output and log files are created there and are only copied back to the output directory when the job finishes or when the job is being monitored in Maestro QikProp 2 0 User Manual Unix 77 Appendix B Command Line Job Control When you run a job from the command line some applications for instance Mac roModel allow you to ask for a job to be run directly in the job s startup dire
68. methylnevanalog 12 388 2 157 2 methyl nevirapine 379 0 896 nabumetone 385 2 217 Nevirapine 405 0 895 dpc27pyridinoneNNRTI 396 2 383 8 chloro TIBO Tivirapine 244 0 893 besipirdine119257 34 250 2 410 bupropion 221 0 891 aminopyrine 75 2 413 thymol 383 0 891 neburon 395 2 440 9 chloro TIBO 504 0 884 triflupromazine 417 2 441 Org12962 399 0 880 Trovirdine PETT 549 2 499 parathion 72 0 880 2 4 6 trichlorophenol 464 2 558 desmethylRTI55 168 0 878 EtEtOPOSEtSEt 300 2 578 estradiol 550 0 876 diazinon 295 2 618 DuPont697 71 0 868 2 3 dichlorophenol 73 2 650 p t butylphenol 75 0 864 thymol 471 2 695 sertraline 462 0 864 rotenone 234 2 706 atrazine 551 0 858 malathion QikProp 2 0 User Manual Unix 91 Appendix C Sample Output Files 92 QikProp 2 0 User Manual Unix Appendix D Sample Input Files D 1 Sample mol File QikProp complies with the MDL SD mol format specified by MDL in J Chem Inf Comput Sci 1992 32 244 255 Sample mol files are provided in the SCHRODINGER qikprop molfiles directory Below are the contents of the flu con mol file in that directory A commentary on the file format follows Diflucan fluconazole WJ BOSS4 2 3D 34 36 0 0 1 0 999 V2000 1 0000 1 0000 0 0000 C 0 0 0 0 0 0 1 6558 1 4713 13367 C 0 0 0 0 0 0 0 3957 043571 0 0000 N 0 0 0 0 0 0 1 7140 1 0274 0 8243 H 0 0 0 0 0 0 0 2102 1 6969 0 2809 H 0 0 0 0 0 dO 2 0649 2 9638 1 2364 C 0 0 0 0 0 0 0 8113 1 2715 2 6136 C 0 0 0 0 0
69. more than the significance cutoff value This value is 0 0006 by default When exactly 37 descriptors and properties are present in the input file e g job name gt CSV if you generated the input file with QikProp QikFit generates a lt jobname gt myfits file QikProp can then use the values in this file to predict the new property for other similar molecules You can use the lt jobname gt myfits file to integrate into QikProp coefficients from your own previous QSPR QSAR analyses This allows you to use those coeffi cients rather than the provided default values to calculate the standard 36 Qik Prop descriptors and properties In addition to the regression analysis described above QikFit can also perform a trend vector analysis This is generally used when there are a large number of descriptors and the ratio of molecules to descriptors is not high For a regression analysis there should be at least five times as many molecules as descriptors QikFit has not been interfaced with Maestro and therefore must be run from a ter minal window See section 9 2 below for more information about executing the program QikProp 2 0 User Manual Unix 55 Chapter 9 OikFit 9 2 Running QikFit To use QikFit from the command line open a terminal window and set the SCHRODINGER environment variable if it has not been set already For more information see section 4 2 Environment Variables on page 15 To run QikFit enter the com
70. n the Plot XY panel as shown 34 QikProp 2 0 User Manual Unix Chapter 5 QuickTopics below Keep this panel open for use in the following exercise in which you will add a scatter plot Plot Settings da N L E w a Zoom 1000 00 100 00 500 00 LA s E 7 Reset Zoom Box Click To Center 33333333333333333333 Drag To Zoon E Figure 5 10 The Plot XY panel QikProp 2 0 User Manual Unix 35 Chapter 5 QuickTopics Creating A Scatter Plot In this exercise you will create a scatter plot of data for all entries in the Project Table and you will explore some additional features of the Plotting Facility 1 Inthe Project Table panel choose Select All from the Select menu 2 Inthe PlotXY panel choose New Plot from the Plot menu The New Series dialog box is displayed This time you will create a scat ter plot to visualize the correlation between two properties Under Plot Name enter Scatter For the x axis property select mol wt and for the y axis property select volume 3 Change the plot style by making selections in the Style of Drawing section For Color choose blue under Line Style select None and for Marker select Cross Click New to generate the new plot Incl r Select or unselect cludes Click t exclude entries Ick to pan project entries Allows selec lected plo
71. nd acebutolol acyclovir alprazolam Xanax alprenolol atropine AZT celecoxib cimetidine Tagamet delavirdineTot E fenfluramine diflucan ibuprofen indomethacin lovastatin lorazepam MKC 442 nevirapine norvasc phenytoin progesterone prozac rimadyl rofecoxib serotonin sustiva telmisartan triflupromazine verapamil viagra zoloft sertraline The results of predictions for the input test CSV file if any are then listed Note that the equation for trend vector predictions is QikProp 2 0 User Manual Unix 87 Appendix C Sample Output Files Pj m tX fo where the f are the trend vector coefficients t is the constant and the x values are the normalized descriptors X5 X X min x max x min C 3 Sample myfits File Below is an excerpt from a sample lt jobname gt myfits file Use this file for your custom QSAR QSPR fits to be output by Qik Prop 2 0 A maximum of 4 fits is allowed For each fit enter the coefficient for each descriptor as a decimal number Fit 1 below is set up as an example to be the same as the log Po w equation used by QikProp for non hydrocarbons Activate it by setting the number of fits to 1 Enter the number of fits on the next line 1 KKKKKKKKKKKKKKXKXXEX XX Fit 1 DE ckockockck ck ckock kc ck ck ck Name for printing 10 characters maximum OPlogPo w constant 0 6789 amine 0 5261 nitro
72. nd relevant machine output Schr dinger E mail help schrodinger com USPS 1500 SW First Ave Suite 1180 Portland OR 97201 Phone 503 299 1150 Fax 503 299 4532 WWW http www schrodinger com FTP ftp ftp schrodinger com When sending e mail messages please include the following all relevant user input and machine output QikProp purchaser company research institution or individual primary QikProp user computer platform type operating system with version number QikProp version number Maestro version number mmshare version number Much of the machine and system information listed above can be produced by entering the command SSCHRODINGER machid at a shell prompt once the SCHRODINGER environment variable has been set 68 QikProp 2 0 User Manual Unix Appendix A Configuring Job Control A 1 Introduction For an overview of the jobcontrol command line utility see Appendix B Command Line Job Control on page 75 Configuration of the Job Control Facility is done in the schrodinger hosts file The default installation of this file is configured to allow running of jobs locally and no action is required by the user However if you want to run distributed jobs run jobs remotely or change the location of the scratch directory where job files are placed temporarily while the job runs then Job Control must be configured The following sections describe how to specify the scrat
73. nd user name from which the user would like to login without specifying a password The list should contain two lines for each machine one with the machine name alone and one with the fully qualified name Your rhosts file should contain entries in the form of lt machinel gt lt your_userid_on_machinel gt lt machinel your_dept domain gt lt your_userid_on_machinel gt The userid in the rhosts file is optional if the userid is the same on the remote hosts You do not need root permission to configure this file but you must make sure that the file does not have group write permission Once you have configured your hosts equiv or rhosts file use the following command to check for success ful communication between the computer that the job will be started on and each of the other computers that the job will use rsh 1 lt your_userid_on_machinel gt lt machinel gt date This command should print the date from the computer lt machinel gt If you have a schrodingerhosts file you can automatically check all of the machines listed in it see A 4 3 Testing the schrodinger hosts File on page 73 A 4 The schrodinger hosts File The Job Control Facility obtains information about the computers hosts on which it will run jobs from the schrodinger hosts file A 4 1 Structure of the schrodinger hosts File A sample schrodinger hosts file is shown below The lines beginning with a are comments and not required OikProp 2
74. nel to another When a new panel is opened it automatically receives picking focus To return to an already open panel and give it picking focus you must move the keyboard focus to that panel and then enable the Pick to lt action gt toggle button where lt action gt is the operation for which you would like to pick atoms Moving the picking focus is called changing the picking mode 3 5 Mouse Functions Within Maestro each button of a three button mouse has a fixed function A sin gle click with the left button is always used for selecting This includes picking atoms bonds and atom groups clicking buttons and selecting menu items The middle mouse button is used to rotate molecules The right button is always used for translating atoms or molecules along the x y or z axis Right clicking on an atom in the Workspace causes that atom to be spot centered in the Workspace Holding down the middle and right mouse buttons in combination is used to zoom in and out on a molecule If you have the handedness on your mouse set to left your mouse functions are the mirror image of those described your right mouse button is used for picking and your left button is used for translating OikProp 2 0 User Manual Unix 11 Chapter 3 The Maestro User Interface 3 5 1 Specialized Mouse Functions in the Project Facility Clicking on project entries with the mouse while pressing the Shift key or the Control key allows you to select any
75. ng data columns from 56 new property data in 56 training set generating 24 Transformation bar 13 trend vector analyses 6 tutorial directory creating 2 V nl 4 W workflow paradigm 10 workflow project based 8 101 Index working directory specifying 20 WPS Ankas innser ao sapian 4 Z ZOOfUM innnan Dee dace pars 11 102 QikProp 2 0 User Manual Unix 1500 SW First Avenue 32nd Floor Tower 45 3655 Nobel Drive Suite 1180 120 West Forty Fifth Street Suite 550 Portland OR 97201 New York NY 10036 San Diego CA 92122 SCHR DINGER
76. o formatted structure file s_m_m2io_version 1 0 0 f_m_ct s_m_title s_sd_MOLNAME s_sd_MDLNUMBER Diflucan fluconazole fluconazole MFCD00004144 m atom 34 First column is atom index i m mmod type QikProp 2 0 User Manual Unix 95 Appendix D Sample Input Files o IA U1 amp wlH Q9 W 9 W W IO NO IO IO DO DO DO IN I2 I2 D O B OG B B B B S S 00 amp amp NF I OUI amp amp N H Lo I o 1 amp amp D h 96 w w 25 41 41 16 25 41 41 25 25 41 41 56 41 56 41 41 42 25 25 41 2 41 r_m_x_coord r_m_y_coord r_m_z_coord i m residue number s m insertion code s m mmod res s m chain name i m color r_m_chargel r_m_charge2 s_m_pdb_residue_name s_m_pdb_atom_name s_m_grow_name i m atomic number i m formal charge S m atom name 1 000000 1 000000 20 000000 0 1 655800 1 471300 336700 0 0 395700 0 357100 20 000000 0 1 714000 1 027400 0 824300 0 0 210200 1 696900 0 280900 0 2 064900 2 963800 236400 0 0 811300 1 271500 2 613600 0 2 876100 20 759000 454800 0 2 929900 3 248500 0 064200 0 2 595300 3 285600 2 134600 0 1 170200 23 586300 185200 0 2 638900 4 076000 0 951800 0 4 145600 2 658600 0 145100 0 3 655900 4 018300 1 790900 0 1 748200 4 677700 1 074600 0 4 567100 3 178000 1 314000 0 5 506700 2 943700 1 800600 0 1 406800 1 308600 3 904000 0 0 595300 1 107500 2 535800 0 0 623400 1 146700 5 062
77. ompare the fast mode results with the normal mode results Notice that in fast mode the dipole moment dipole dipole volume d2ov the ionization potential ip and the electron affinity ea are not predicted Instead 0 0 is entered for these values This is because in the interest of saving time the PM3 single point calculation is not performed Notice also that the predictions for the free energy of solvation terms log pc16 log pw and log po w differ between fast and normal processing modes because in fast mode the QSPR equations are refit without the dipole terms QikProp 2 0 User Manual Unix 27 Chapter 5 QuickTopics Project Table table scratch Project Table Select Selection Total Entries 400 Subset Entries ui 400 Selected Entries 400 Entries m z Properties Al FERE p J Co SW mol 0004 385 959300 0 831 249 694756 4 068 6 39 2 67 0 16062 mol 0004 1 385 959300 0 831 249 694756 4 068 0 00 0 00 0 16062 nol 0007 1114 45286 0 062 740 632662 3 559 6 33 1 99 0 34287 nol 0007 1 1114 45286 0 062 740 632662 3 559 0 00 0 00 0 34287 mol 0008 2256 30705 0 149 1532 11987 2 398 7 33 2 84 0 00688 nol 0008 1 2256 30705 0 149 1532 11987 2 398 0 00 0 00688 A Synchronize Workspace Changes J Mark Selected Entries Hide Figure 5 8 The Project Table with fast and normal mode properties sorted
78. on Output and Commentary The following is an example of a jobname out file produced by performing a Qik Fit linear regression In this example we fit to the last descriptor instead of adding an experimental value for QikFit to fit to Commentary on the file contents is pro vided in bold OikFit 2 0 Multiple Linear Regression Analysis Incomplete Incomplete Incomplete Incomplete Incomplete entry skipping molecule entry skipping molecule entry skipping molecule entry skipping molecule entry skipping molecule Illegal Character in Descriptor CMC00000004 CMC00000047 CMC00000152 CMC00000160 CMC00000163 If an entry in the CSV file is incomplete missing the activity or the value for a descriptor or if the file contains an illegal character the entry is ignored and a notice is printed at the top of the file Column 19 21 23 25 27 29 31 33 35 37 Simplex exceeded maximum cycles Contents Column molecule 2 amine 4 acid 6 rotor 8 CNS 10 dipole 12 FOSA 14 PISA 16 volume 18 accptHB 20 ACxDN 5 SA 22 QPpolrz 24 QPlogPoct 26 OPlogPo w 28 BIPCaco 30 QPlogBB 32 OPlogKp 34 EA eV 36 OPlogKhsa 38 QikProp 2 0 User Manual Unix Contents stars nitro amide rctvFG MW SASA FISA WPSA donorHB dip 2 V glob QPlogPC16 QPlogPw OPlogS AffyPCaco AffyPMDCK IP eV metabol exp_data 9000 81 Appendix C Sample Output Files Regression did not converge in
79. ored from Maestro s Monitor panel For information on the Job Control Facility and how to use the Facility to monitor QikProp jobs see Appendix B Command Line Job Control on page 75 8 3 Input Files QikProp input must be a file containing the 3D structure x y z coordinates and atomic numbers of one or more molecules Four file formats are accepted Maestro formatted mae files MDL mol files also known as 3D SD files PDB files e BOSS MCPRO Z matrix files An example of each file type is provided in the SCHRODINGER qikprop v lt version gt molfiles directory In addition this subdirectory contains the mol files for 30 common drugs See section D 1 Sample mol File on page 93 for more information about the SD mol file format QikProp input structures and files must meet the following criteria Hydrogens on input structures must be explicit You cannot therefore use as input united atom typed files from molecular mechanics pro grams If you attempt to use structures with the united atom hydrogen treatment Maestro will prompt you to use an alternative hydrogen treatment There is no such check for missing hydrogens when you run QikProp from the command line With the exception of delimited MDL SD mol files and Maestro formatted files each structure file must contain only one molecule You can concatenate MDL SD mol lt jobname gt mol files into a sin gle file for input to QikProp For an example se
80. r Constant 4 186 Total 0 054 Total 2 073 200 molecules vere successfully processed 0 failed Monitor Pause Stop Update betach Resune KU Delete W Show Jobs From Current Project Only incorporated home heather schrodingeg Figure 5 6 The Monitor panel displaying output from the ligands job When the job is complete the following files should be in your working directory ligands out mae ligands qpsa e ligands mae ligands CSV e ligands out ligands warning The file ligands out mae is a Maestro formatted file that contains property data and structural information The ligands mae file is written by QikProp at the start of the job and contains only structural information for the selected entries The ligands out file lists properties predicted and the limits specified in OPlimits It also includes a section that shows how some of the properties were formed by lin ear combinations of more basic molecular properties The ligands gpsa file pro vides a detailed surface area analysis and ligands CSV contains all the predicted properties for each structure in comma separated value CSV format The lt filename gt warning file is produced only when QikProp encounters prob lems with one or more of the input structures In this test case all structures were processed successfully However results for three of these structures might not be valid because one of the processed st
81. r convenience you might want to add SSCHRODINGER to your PATH definition This allows you to run Maestro QikProp QikFit and QikSim by sim ply typing their script names in a terminal window once SCHRODINGER has been set QikProp 2 0 User Manual Unix 15 Chapter 4 Launching the Programs In some cases the DISPLAY environment variable is set automatically upon login If it isn t you must either set it automatically by adding the DISPLAY vari able definition to your login shell script cshrc or login file for csh or profile file for bash or ksh or set it manually each time you launch the program from a new terminal window To set the DISPLAY environment variable use the appropriate version of the following command substituting the name of the display machine for machine name To determine the name of a display machine type host name in a terminal window csh setenv DISPLAY lt machine_name gt 0 0 bash amp ksh export DISPLAY lt machine name gt 0 0 4 3 Launching QikProp from Maestro Before you can run QikProp from Maestro you must first launch a Maestro ses sion To launch QikProp from Maestro 1 Inaterminal window enter the command SSCHRODINGER maestro 2 In Maestro s Main Application Window choose QikProp from the Applications menu The QikProp panel is displayed For informa tion about submitting a QikProp calculation using this panel see Chapter 6 Maestro QikProp on page 41
82. rences prefe TT Delete Markers Font Size Project Di rectory House File suffix Default directory for job startup and file i o Maestro s current vorking directory Parent of project directory Project directory x Project jobs directory x Other specify below Directory currentdir Figure 7 1 The Directory folder of the Preferences panel QikProp 2 0 User Manual Unix 49 Chapter 7 QikProp Output The default file i o directory is Maestro s current working directory To change the file i o directory preference open the Preferences panel from the Maestro menu in the Maestro Main Application Window Then click the toggle button cor responding to the desired directory option Click Hide to close the panel Note that the default file i o directory as well as most of the other directory Pref erence choices is relative For instance if you select the Maestro s current working directory option Maestro will write output files to the directory from which you launched Maestro unless you have since entered the cd or chdir command in the Command Input Area 50 QikProp 2 0 User Manual Unix Chapter 8 Command Line QikProp 8 1 Introduction QikProp can be run from the command line as well as from the Maestro user inter face You might want to run QikProp from the command line in the following sit uations When you want to simultaneously process more than 500 structures When you
83. rimental value that you have added in the training file it generates a lt jobnname gt myfits file This file can be used with QikProp to predict the new property for additional structurally similar molecules In addition a lt jobname gt log file is produced This file con tains basic information about the job such as what options were specified 9 7 1 The lt jobname gt out File The lt jobname gt out file contains results from the iterative cycles QikFit performs to determine which descriptors in the input file have linear relationships with the new property The last line of the file contains the predicted new property for the structures in the test file if one was provided Excerpts from the file SCHRODINGER qikprop v version tutorial qikfit ligands out are provided for both a regression analysis and a trend vector analysis See Appendix C Sample Output Files on page 81 for the excerpts 9 7 2 The lt jobname gt myfits File This file contains coefficients which when used with QikProp descriptors and properties can be used to generate the new experimental property for molecules that are structurally similar to those in the training set OikProp 2 0 User Manual Unix 59 Chapter 9 OikFit A lt jobname gt myfits file is only written during a QikFit run when there are exactly 37 descriptors and properties 36 default QikProp descriptors and proper ties and the additional experimental activity column you have a
84. rte RC e Rite 55 92 Running Qik Pit t deti Saati qae due 56 9 3 The Training Fil iR tentes 57 YA The Test File 2 222 t e tate et etu sr ete 58 9 5 Significance Cutoff Values e ener 58 9 6 Running on a Remote Host eene 59 9 T Output Files 5 2 erat to E OE oet fatte ageret aseo 59 9 7 1 The lt jobname gt out File penoso otini 59 9 7 2 The lt jobname gt myfits File oo ececeseeeeereeseecnseceeeeeeeeeeeees 59 9 8 Using QikFit Output To Predict New Properties sss 60 Chapter 10 QIKSIn aussen 61 10 14 Introduction 5 5 ire etos e ees 61 10 2 Command Syntax cientes ette adducit 61 10 5 Inp t 2 2 22 82 RER E ete idee edd 62 Chapter 11 Bibliography 2 000 65 LI EQIKProp one ie eet t donee 65 TT 2 OIKFit nn nan seat sand an wea nas 65 Chapter 12 Help sinne 67 12 1 Getting Help on Program Installation 67 OikProp 2 0 User Manual iii 12 2 Getting Help from within Maestro 67 12 3 QikProp Help from the Command Line sese 68 12 4 Technical Support Seas HR 68 Appendix A Configuring Job Control 69 AA Introduction iir m bed ab RE RE eG eso tede 69 A 2 The Location of the Scratch Directory eee 69 A 3 Preparing for Remote Job Submission 70 A 4 The schrodinger hosts File
85. ructures is not neutral and two of the struc tures contain ammonium ions For more information on output files see Chapter 7 QikProp Output on page 47 6 Savea copy of the project by choosing Copy Project To from the Project menu in the Main Application Window Name the project ligs prj and click Copy QikProp 2 0 User Manual Unix 25 Chapter 5 QuickTopics Running QikProp in Fast Processing Mode In this exercise you will run QikProp in fast mode You will use the same set of structures you processed in normal mode in the previous exercise so that you can compare the output files produced by each mode 1 Choose Save Scratch Project from the Project menu of the Main Application Window enter comp prj under Project and click Rename The current scratch project is now named comp prj 2 Copy the file QPlimits from the SCHRODINGER gikprop v lt ver sion gt data directory into the working directory 3 Open the QPlimits file with a text editor Below is an excerpt from the file Molecular Weight standard is 130 0 725 0 130 04 725 0 Dipole Moment D standard is 1 0 12 5 1 0 7 12 5 QP log Khsa Serum Protein Binding standard is 1 5 1 2 er Be 1 2 QP log BB for brain blood standard is 3 0 1 10 3 0 1 0 Mode std or fast std The first portion of the file contains the default limit settings These can be edited to suit your needs In this exercise you do not need to modify th
86. ry SCHRODINGER gikprop v lt version gt docs where version is the five digit version number of your QikProp installation 2 2 QikFit QikFit generates optimized regression equations for the correlation of experimen tal data with sets of descriptors such as those generated by QikProp QikFit out put can then be used by QikProp to predict the experimental property for any number of additional structurally similar molecules Alternatively QikFit can be used independently from QikProp In addition to regression analysis QikFit can perform trend vector analyses Trend vector analysis is generally used when there are a large number of descriptors and the ratio of molecules to descriptors is not high For regression analyses this ratio should be at least five There is currently no Maestro interface for QikFit This module must be run from the command line 2 3 QikSim QikSim performs similarity diversity analyses on structures in the input file based on Euclidean distances and Tanimoto coefficients All included structures are ranked in comparison to a user specified probe molecule Output from QikProp can be used as input for QikSim There is currently no Maestro interface for QikSim This module must be run from the command line 6 QikProp 2 0 User Manual Unix Chapter 3 The Maestro User Interface 3 1 The Maestro Main Application Window When you start Maestro the Main Application Window is displayed Figure 3 1 This
87. s OikProp 2 0 User Manual Unix 73 Appendix A Configuring Job Control 74 QikProp 2 0 User Manual Unix Appendix B Command Line Job Control B 1 Introduction The SCHRODINGER jobcontrol utility allows you to perform a number of job control tasks from the command line You can perform many of these tasks using the Maestro Monitor panel as well but some things such as purging the jobs database can only be done using the jobcontrol utility B 2 Jobcontrol Syntax and Supported Commands The syntax for jobcontrol utility commands is SSCHRODINGER jobcontrol command job selection where commands is the command for the operation you want to perform and job selection is the name of the specific job if applicable The command can be one of the following Command Action list the jobld job name and status show show the complete job record kill terminate the job immediately stop ask the job to stop itself as soon as possible bmin only pause suspend the job temporarily resume continue running a paused job monitor lt n gt ask for monitoring files to be sent every n seconds cancel cancel a job that has been launched but not started purge remove a completed job from the database help describes the jobcontrol commands For example to list all currently running jobs you would enter the command SSCHRODINGER jobcontrol list Q
88. sociated with an entry the Vis column of the Project Table remains empty 8 QikProp 2 0 User Manual Unix Chapter 3 The Maestro User Interface Project Table table hone laurie ligs prj I Table Select Selection Total Entries 200 Subset Entries 200 Selected Entries 2 Entries A Properties Abi An ncs etry Cr a Selected mol 0007 mol 0007 es entries 7 nol 0008 mol 0008 Synchronize Workspace Changes Mark Selected Entries Hide Help Figure 3 2 The Project Table panel The Project Facility allows you to operate on these entries You can choose which entries to include in the Workspace by checking the corresponding In box on the Project Table panel Including an entry causes any structures associated with that entry to be rendered in the Workspace You can exclude a structure by clearing the check box You can select an entry or entries to use as input for a QikProp job or you can use the entry or entries in the Workspace In addition you can select entries as input for the ePlayer which displays in sequence the selected structures Additionally you can select entries on which to operate using other features such as Dupli cate Combine Rename or Sort When you build molecules in the Workspace they constitute the scratch entry until you choose to save the structures as project entries The scratch entry is not saved
89. t in Workspace Pan plot i selected plo p tionofzooming in the ai tool in the given de area in plot direction Label or unlabel LA plot points Plot XY plotxy pre me se Diamonds i 5100 00 denote 1 1600 00 4 F structures 1 included in i 1200 00 4 the Work Click to space reset zoom settings 400 00 1 Zoom Box 1 1 Click To Center H Drag To Zoom P0000 7 1 3 Dashed BERBERBELRELEEEEEEEEEEE n nl Entry Name t 0 00110 00 330 00 550 00 FE line 1 mol wt 1 SASA sasa vs Entry Name t Scatter volume v3 mol wt F denotes Hide selected plot Figure 5 11 Plot XY panel 36 QikProp 2 0 User Manual Unix Chapter 5 QuickTopics The icons at the top of the PlotXY panel can be selected to change the mouse function within that panel You can choose to select or include Project Table entries in the Workspace by clicking on points within a plot For instance clicking on the E icon in the toolbar of the Plot XY panel and then clicking on the point in the plot which has the largest SASA value causes a diamond shaped marker to appear around the point in the plot The structure is also included in the Work space Additional structures can be included in the Workspace by holding down the SHIFT key and clicking on other points in the plot These can be excluded from the Workspace by choosing the Bf icon in the toolbar and clicking points in the plot The dashed line surround
90. t edit the file and delete the columns Z Perform a trend vector analysis rather than the standard regression analysis 56 QikProp 2 0 User Manual Unix Chapter 9 QikFit HOST host Run the job on the specified remote host WAIT Run the job in the foreground do not return to the command prompt until the job ends The default is to run the job in the background return to the command prompt immediately 9 3 The Training File To use QikFit to predict an additional property you must have experimental data for enough compounds to comprise a training set with which regression equa tions can be generated For a regression analysis it is recommended that you have five times more training compounds than descriptors approximately 175 com pounds If you have fewer compounds than this it is recommended that you per form a trend vector analysis rather than a regression analysis The training file must contain molecular properties and descriptors as well as the new experimental property values for all of the structures Requirements for the Training File Format The training file must be in CSV format If you are using as a training file lt jobname gt CSV generated by QikProp this file is already in CSV format To this file you must add a column containing the new experi mental property values The first line must be a header with names for the columns The second and subsequent lines must contain a molecule
91. t sea 10 pick Sites solta S 10 PIERIT seen 10 picking mode sun 11 PIS Ar teste 4 Plot XY Panel sut dense 35 Preferences panel 49 project entries sorting 27 Project Facility introduction to 8 Project Table panel c scd oes 23 BIOS een C USE 8 properties and descriptors Hader 4 HATE sans 4 RATE nahen 4 metabol 4 2 4 aee 5 DEPO iia eres IE ICE asia PIERRE PERS 4 SEGUE aan 4 HOTOT een et 4 MISTAS ensure 4 Tes do Baar 5 ACXDN S S nes 5 Ally PC dO srt ii al dass 5 AffyPMDCK crues 5 BIP CACC ee 5 CNS astecas sie esess Ertl 4 100 dip asda tios itunes 5 pole eot roots 4 donorHB uni 5 EA eV area 5 PIS AC sr etienne 4 FOS Annee 4 Plo esee su oda ndi one e 5 IP ey rit RPE SR nde vete 5 Molecule name s issus 4 MW under 4 PISA near ren 4 PrOpErtiES ans 4 OPIOSBB re te ame 5 QPlogKhs desire 5 OPIGEKD une are 5 OPISSPOTGa sen 5 OPIOBPOW Sins ane 5 OPlogPOoGt iini des 5 PIO BPW ee 5 OPIOBB ae 5 Opal 5 SAS A URBEFRPPEPEFEEUEPEBE PEFPELPEPRIEPPIEFUR 4 WPSA eene rendre 4 properties plotting 34 properties predicting 39 Q QikFit myfits file issus 59 OU He ee ee 59 launching ae caes 17 DUNN ee 31 56 significance cutoff values 58 test He oo Rn INO EG 58 rainhas da een 57 qikfit command AFSUMENIS cese cse P 56 Hel prot eot dae torto 68 HOST option 59 SYMUAK he ie 56 QikProp 2 0 User Manual Unix WAIT
92. tep must be performed each time a job is launched on a remote host The first two steps are described in section A 3 Pre paring for Remote Job Submission on page 70 and section A 4 The schrod inger hosts File on page 71 When you submit a QikProp job from Maestro use the Hosts option menu on the QikProp panel to select a host on which to run the job AII hosts that have been configured in the schrodinger hosts file appear on this menu 42 Select a host from those available by clicking on a name on the Hosts menu zilda QikProp gikprop Hosts localhost Source MO Work juliet beatrice J uma erica Selected Entries Into Project By ntries gt Replacing Existing Entries gt Ignoring Output Login heather Figure 6 2 The Hosts menu on the QikProp panel QikProp 2 0 User Manual Unix Chapter 6 Maestro QikProp 6 4 Using the QPlimits File The OPlimits file can be used to run QikProp in fast processing mode or to cus tomize the ranges of values that determine which molecules are to be flagged as being dissimilar to other known drugs The file can be copied from the SCHRO DINGER qikprop v lt version gt data directory and placed in the present working directory or in SHOME schrodinger qikprop By default the molecules are flagged as being dissimilar to other known drugs based on comparison to a set of test structures studi
93. ter Significance Partial F Partial R 2 MW 0 001468 0 0022 4 5926 0 0227 SASA 0 003312 0 0380 5 4411 0 0267 volume 0 001932 0 0374 6 1115 0 0299 ACxDN 5 SA 2 233578 0 0000 1 2437 0 0062 QPpolrz 0 051634 0 0276 6 1028 0 0299 QPlogPC16 0 181576 0 0265 2 5284 0 0126 QPlogPoct 0 016400 0 0009 0 9059 0 0046 QikProp 2 0 User Manual Unix 83 Appendix C Sample Output Files OPlogPo w 0 142958 0 0013 4 2445 0 0210 OPlogKp 0 160990 0 0048 0 2152 0 0011 Constant 0 378240 0 0021 The cycles continue until no more descriptors fall below the significance cut off or until 10 cycles have been performed The present case terminated on the third cycle Out of the original 37 descriptors 8 have been retained Regression Analysis Cycle 3 R Squared 0 0775 RMS Error 0 8303 Average Error 0 5826 Sum of Squares 136 5122 F Statistic 2 0054 Degrees of Freedom 8 No of Data Points 200 Average Activity 0 9447 Exptl Activ Range 2 8760 to 2 7062 Calcd Activ Range 0 4929 to 1 7123 Activity in Column 38 Signif Cutoff 0 0006 Descriptor Parameter Significance Partial F Partial R 2 MW 0 001697 0 0030 4 5926 0 0227 SASA 0 003658 0 0464 5 4411 0 0267 volume 0 002134 0 0456 6 1115 0 0299 QPpolrz 0 052912 0 0290 6 1028 0 0299 QPlogPC16 0 182341 0 0267 2 5284 0 0126 QPlogPoct 0 014890 0 0008 0 9059 0 0046 QPlogPo w 0 152722 0 0014 4 2445 0 0210 QPlogKp 0 161398 0 0048 0 2152 0 0011 Constant 0 386967 0 0022
94. that are new in this release see the QikProp 2 0 Release Notes For more information on using Maestro see the Maestro online help or the Maestro User Manual For technical information on the accuracy of QikProp see the QikProp 2 0 Technical Information document 1 2 Document Conventions Throughout this manual reference is made to Maestro GUI components such as panels buttons toggle buttons radio buttons Sidebar options menus and menu options GUI components whose labels appear in the GUI are set in Helvetica Elements that are not labeled in the GUI are capitalized but not set in Helvetica In addition to GUI components the names of keyboard keys are set in Helvetica Machine input and output are set in Courier File names command script names and entry names are set in italics Directory names and project names are set in bold The QuickTopics chapter of this manual contains exercise sets that are intended to provide fast streamlined instruction for performing common QikProp tasks Each of these QuickTopic exercise sets begins with the icon In this document to type a command means to type the required text in the speci fied location and to enter a command means to type the required text and then press the Enter key The environment variable SCHRODINGER is used for the directory in which your Schr dinger software is installed QikProp 2 0 User Manual Unix 1 Chapter 1 User Manual Overview 2 QikProp 2 0 User Manual
95. the Main Application Window open the QikProp panel from the Applications menu 2 Inthe Job text box of the QikProp panel type ligands E QikProp qikprop Job ligands Login laurie Hosts localhost Source Of Job Input Workspace Selected Entries Incorporate Output Into Project By gt Appending New Entries Replacing Existing Entries gt Ignoring Output Start Hide Help Figure 5 4 The QikProp panel 3 Choose Selected Entries for the Source of Job Input setting 4 Choose Replacing Existing Entries under the Incorporate Ouput Into Project By heading 5 Click Start The Hydrogen Lone Pair Fixup panel is displayed Entry mol 0039 does not have all the required hydrogens for a QikProp calculation Hydrogen Lone Pair Fixup Suitable treatments are listed below choose one of these and then the Fix button if you want to fix this before starting the job All atom with No L W Make this treatment the default for this session Fix Mismatch Fix For All Don t Fix Don t Fix For All Cancel Job Figure 5 5 The Hydrogen Lone Pair Fixup panel You must choose to fix the input because QikProp results are not valid for input structures that are missing hydrogens Click Fix For All The Monitor panel is displayed and the job begins running 24 QikProp 2 0 User Manual Unix Chapter 5 QuickTopics Fl Monitor monito
96. tive functional groups the specific groups are listed in the lt jobname gt out file The presence of these groups can lead to false positives in HTS assays and to decomposition reactivity toxicity problems in vivo CNS Predicted central nervous system activity on a 2 inactive to 2 active scale MW Molecular weight of the molecule dipole Computed dipole moment of the molecule SASA Total solvent accessible surface area SASA in square ang str ms using a probe with a 1 4A radius FOSA Hydrophobic component of the SASA saturated carbon and attached hydrogen FISA Hydrophilic component of the SASA SASA on N O and H on heteroatoms PISA rt carbon and attached hydrogen component of the SASA WPSA Weakly polar component of the SASA halogens P and S volume Total solvent accessible volume in cubic ngstr ms using a probe with a 1 4 radius 4 QikProp 2 0 User Manual Unix donorHB accptHB dip 2 Vt ACxDN 5 SA glob QPpolrz QPlogPC16 QPlogPoct QPlogPw QPlogPo w QPlogS BIPCaco AffyPCaco QPlogBB AffyPMDCK QPlogKp IP ev t EA eV t metabol QPLog Khsa Chapter 2 The OikProp Product Family Estimated number of hydrogen bonds that would be donated by the solute to water molecules in an aqueous solution Estimated number of hydrogen bonds that would be accepted by the solute from water molecules in an aqueous solution Square of the dipole moment divided by the molecular vol u
97. tructural information for the molecules to be evaluated The structure contained in the lt jobname gt mae file depends on the Source of Job Input setting If you selected Workspace in the QikProp panel the lt jobname gt mae file contains any structures that appeared in the Workspace when the job was started If you selected Selected Entries the file contains the structures corresponding to the entries in the Project Table that were selected when the job was started QikProp 2 0 User Manual Unix 47 Chapter 7 QikProp Output 7 1 3 The lt jobname gt gpsa File The lt jobname gt gpsa file contains additional information for each molecule including the covalent neighbors list atom type assignments associated atom type force field parameters and a solvent accessible surface area SASA analysis At the end of the file there is a summary giving the number of molecules that were successfully processed and the number of molecules that were not success fully processed and a report of the processor time used 7 1 4 The lt jobname gt out File The lt jobname gt out file lists the output descriptors and predicted properties In addition the file contains results from comparisons between the compound s properties and the properties of typical drugs Each property with a value outside the 95 range for known drugs is marked with an asterisk Also in the lt jobname gt out file is a QP Breakdown section for each structur
98. tt beet ea tet s 39 Chapter 6 Maestro QikProp esee ee eee eerte ee eene eee ne seta a 41 6 1 Opening the QikProp Panel ss 41 6 2 Naming the QikProp Job essere 41 6 3 Selecting a Host Computer ss 41 6 4 Using the QPlimits File ss 43 6 5 Specifying an Input Source ss 43 6 6 Selecting a Job Output Incorporation Scheme sussse 44 6 7 Starting a QikProp Job sic necesiten NEA EEEE EELA 44 6 5 Monitoring the Job estie nen Be aan 45 Chapter 7 QikProp Output c ecce ee eere ee ee etes ee ete see enus 47 Pol Output File Types ere RH RE ERR REESE TR EAE e Ne da 47 7 1 1 The lt jobname gt out mae File essere 47 7 1 2 The lt jobname gt mae File rsson ee iiien 47 QikProp 2 0 User Manual 7 1 3 The lt jobname gt gpsa File eee 48 7 1 4 The lt gobname gt out File ae edite eter e pets 48 7 1 5 The lt jobname gt CSV File wo cee ceceseeseeseceeeeeseecesecnseeseeeeneeees 48 7 1 6 The lt jobname gt warning File eeeeeeeeeseecnseceeeseeeeneeees 49 7 2 Output File Directory eret ea ARE en ehe eget 49 Chapter 8 Command Line QikProp eee eere e eene 51 8 1 Introduction nen aan 51 8 2 Issuing the qikprop Command eene 51 9 3 Input Files no eo tne dee toe qa tt coetum 52 Chapter 9 OIKEM nn aussen 55 9 1 Introduction Hors
99. ult is 0 which selects the last row n lt nkeep gt The number of most similar molecules to report By default all are reported HOST host Run the job on the specified remote host WAIT Do not return to the command prompt until the job finishes The default is to run the job in the background QikProp 2 0 User Manual Unix 61 Chapter 10 OikSim 10 3 Input A QikSim analysis requires three input elements 1 A lt jobname gt CSV file written by version 2 0 of QikProp A sam ple CSV file is provided in the directory SSCHRODINGER qiksim v1 0 testcases This file contains QikProp 2 0 results for 555 molecules most of which are known drugs A limits file containing the limits and weights for each QikProp descriptor that is used for the QikSim similarity diversity analy sis molecule is output as similar or dissimilar if each of its Qik Prop descriptors falls between the listed minimum and maximum values Otherwise the molecule does not appear in the output The weights can be used linearly to emphasize or de emphasize the contri bution of a descriptor to the similarity dissimilarity measure The file begins with Descriptor min max Stars 0 1000 Amines 0 1000 Nitro 0 1000 Acid 0 1000 Amides 0 1000 Rotor 0 1000 etc 62 Number o 0 0 0 0 Number o 0 0 Number o 4 0 Number o 0 0 Number of weight stars non conjugated amines nitro groups carboxylic a
100. wing files should be in your working directory e est out mae fest qpsa fest mae fest CSV e tfest out You will use the test CSV file in the QikFit run in the following exercise 30 QikProp 2 0 User Manual Unix Chapter 5 QuickTopics Running QikFit In this exercise you will use QikFit to predict the new exp_data property for the test structure mol_7147 whose other properties were predicted in the previous exercise 1 To predict the exp data property run QikFit by typing the follow ing command in a terminal window SSCHRODINGER qikfit t test CSV training CSV By default QikFit treats the last column in the training file as the new experimen tal value If you want to specify a different column you can do so with the a option When the job is finished the following files should be in the directory from which you launched QikFit e training myfits e fraining out e training log The file training out includes the parameter values calculated during each cycle of the regression statistical data for each cycle and a list of the experimental and calculated values for each compound An excerpt from the training out file is shown below N Exptl Activity Calculated Delta Compound 1 1 331762 1 206324 0 125437 mol 0004 2 1 217879 1 142674 0 075205 mol 0007 3 0 248979 1 046550 0 797572 mol 0008 199 0 856038 1 145599 0 289561 mol 3085 200 1 838763 1 177887 0 660876 mol 3138 Final Parameter Values

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