XLOGP3 v 3.2.0 User Manual
Contents
1. XLOGP3 v 3 2 0 User Manual Copyright by Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 2007 Table of Contents ly Overview 0m XLOGP3 pce ide cle tee ted celine pile een adel tie We alien tds neni 1 2 gt Program NISC ALTA OD cesta EE 3 2A System Reg irementS urte eignet reres t rgita i shes tate e geis a aeS 3 2 2 Installation sssini puedes Ade EE Ee 3 SR ENEE 5 Sul Ee WEE 5 3 2 Screen a Compound Library ccissscassssecssadssessncsasnneztenss Sssunadonsacdesnsveveannccaanelebeneseaunceegenees 6 3 3 Howto Use XLOGP3 EE 6 3A Process M l ple TE 7 3 3 Propran Outputs casen a a E eee 8 3 6 Warning and Error Meeting Eed EE 9 4 On Additional Knowledge Sets viisisesssdivssaccevasecesacacvenacessndenieaspevarvesevsncteasacadeadeesiedsoractens 10 4 1 nemei 10 4 2 Supply Additional Knowledge Sets snseeseeseeeseseeeseseresresseserssressessrssresserseesressreseee 11 5 On line Demo of XLOGP3 noiril siin ees etn eed ad eee 11 6 Appendix Definition of Druglikeness Dropertes ee ese eeseceeeceeeeeeseecsaeceeeteeeeeneees 12 Contact Information een eh E E OE E es eee 13 ee e 13 XLOGP3 User Manual 1 OVERVIEW ON XLOGP3 The logarithm of the partition coefficient between n octanol and water also referred to as logP has been widely used in quantitative structure activity relationship QSAR studies as a key parameter for characterizing lipophilicity We have developed a new method i e XLOGP32. saved in result_df2 txt xlogp3 p test mol2 result_df2 txt Example 3 The following command will use test TTDB as an additional knowledge set for logP calculation Results are saved in result_df_ex1 txt xlogp3 test mol2 result_df_ex1 txt test TTDB A more convenient way of utilizing user provided knowledge sets is to make a copy of the database file here test TTDB in parameter subdirectory then execute xlogp3 test mol result_df_ex2 txt You will see the result i e result_df_ex2 txt is identical to that of result_df_ex1 txt Actually all the files under parameter subdirectory with the extension of T TDB will be regarded by XLOGP3 as a knowledge set detailed information can be found in Section 4 Example 4 The following command will screen a compound library i e test mol2 All compounds that satisfy the restrictions defined in example rule will be output as test_OK mol2 xlogp3 s test mol2 test_OK mol2 example rule 3 4 Process Multiple Files For the sake of convenience XLOGP3 can handle several files under the same directory at one time by supporting wildcard Each file can contain single or multiple molecules The following command will calculate logP for files under yourDIR subdirectory Note only supported formats described in Section 3 1 will be processed otherwise skipped xlogp3 yourDIR outputResultFile 7 Latest revision Dec 2007 XLOGP3 User Manual Please note the couple of double quotat
3. as knowledge set 5 ON LINE DEMO OF XLOGP3 XLOGP3 Online Your Motecues RT Supported Formats EEA Optional Druglikeness Properties Reference Tiejun Cheng Yuan Zhao Xun Li Fu Lin Yong Xu Xinglong Zhang Yan Li and Renxiao Wang Computation of Octanol VVater Partition Coefficients by Guiding an Additive Model with Knowledge J Chem Inf Model accepted You are the bIDIDIDIEIDT visitor of this page Figure 4 On line Demo of XLOGP3 XLOGP3 is available for on line testing via the web server of Computational Chemical 11 Latest revision Dec 2007 XLOGP3 User Manual Biology Group CCBG at http www sioc ccbg ac cn software xlogp3 User can submit a job through web Figure 4 by uploading molecules in either of MOL2 SDF RDF MOL or MDL formats In addition to logP calculation some optional druglikeness properties such as molecular weight number of hydrogen bond donors and acceptors number of rotatable bonds and etc Results can be downloaded once the job is finished Figure 5 File Name File Size test sdf 18 23 KB File Name File Size xlogp3 6993 logp dE ue xlogp3 6993 err OB Figure 5 Results of an Job Submitted On line 6 APPENDIX Definition of Druglikeness Properties in XLOGP3 lt Hydrogen Bond Donor sp3 hybridized nitrogen or oxygen atom with at least one hydrogen atom e g OH NH NH2 NH lt Hydrogen Bond Acceptor sp2 hybridized oxygen atom in a carbon
4. exist create one 4 Latest revision Dec 2007 XLOGP3 User Manual 3 PROGRAM USAGE 3 1 Getting Started The general synopsis for using XLOGP3 is xlogp3 p v inputMoleFile outputResultFile ex TTDB XLOGP3 requires two necessary parameters i e inputMoleFile and outputResultFile and two optional parameters i e pv and exTTDB Parameter inputMoleFile is the input filename containing molecules to be calculated File extension of inputMoleFile is very important but case insensitive because XLOGP3 will judge an input file format according to its file extension The SYBYL MOL2 and MDL SDF MOL MDL RDF formats are currently supported The MOL2 and SDF formats are recommended Parameter outputResultFile is the output filename containing calculation results Parameter yv will give full information of program s output otherwise the simplest If you are dealing with a large database turn off this parameter can cut down the output to minimum If optional parameter p is provided XLOGP3 will also calculate some druglikeness properties such as molecular weight number of hydrogen bond donors and acceptors number of rotatable bonds and number of rings detailed information can be found in Section 6 1 Another optional parameter exTTDB indicates a user in house knowledge set if not provided XLOGP3 will search only in default knowledge set detailed information can be found in Section 4 A so called file xlogp3 log will be created under c
5. AA 0 847 0 80 0 57 ALOGPS 0 908 0 60 0 42 CLOGP 0 838 0 88 0 51 TOPKAT 0 815 0 88 0 56 AlogP98 0 802 0 90 0 64 XLOGP2 0 777 0 95 0 68 KOWWIN 0 771 1 10 0 63 HINTLOGP 0 491 1 93 1 30 Correlation coefficients T Root mean squared error between experimental and predicted values Mean unsigned error between experimental and predicted values XLOGP3 pure atom additive model The test set is contained in the training set of ALOGPS Table 2 Results of Some logP Methods on 219 Oligo peptides Models R RMSE MUE XLOGP3 0 932 0 32 0 24 XLOGP3 0 758 0 71 0 55 XLOGP3 AA 0 824 0 72 0 59 PLOGP 0 832 0 46 0 28 ALOGPS 0 765 0 73 0 54 TOPKAT 0 706 0 74 0 43 CLOGP 0 536 0 97 0 75 AlogP98 0 086 2 07 1 62 XLOGP2 0 078 2 24 1 78 KOWWIN 0 075 2 18 1 70 HINTLOGP 0 007 2 92 2 34 When peptides are included in the knowledge set When peptides are not included in the knowledge set The algorithm of XLOGP3 is developed by collaborations between Prof Renxiao Wang s group at the Shanghai Institute of Organic Chemistry Chinese Academy of Sciences and Prof Luhua Lai s group at the College of Chemistry Peking University The full copyright of XLOGP3 is held by the Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 2 Latest revision Dec 2007 XLOGP3 User Manual 2 PROGRAM INSTALLATION 2 1 System Requirements XLOGP3 is a command line oriented program It can be executed in a shell teg C shel
6. ING 0 10 Figure 2 An Example of filtering rules This file is designed as flexible as possible so that users can build their own rules very easily Note lines start with the character will be ignored by program so the users can comment out one or more rules by adding a as the starting character of that lines 3 3 How to Use XLOGP3 There are 3 files under example subdirectory test mol2 test TTDB and default rule File test mol2 contains 6 small molecules for testing File test TTDB is provided as additional user knowledge set which contains structural information and experimental logP value of the molecules in test mol2 File default rule defines filtering rules as shown in Figure 2 In the rest part of this section we will show some examples of using XLOGP3 with theses files For your convenience please copy them into your working directory Example 1 The following command will calculate the logP values of the molecules in 6 Latest revision Dec 2007 XLOGP3 User Manual test mol2 using default TTDB this file locates in parameter subdirectory as the default knowledge set Results with detailed information are saved in result_df1 txt xlogp3 v test mol2 result_df1 txt Example 2 In addition to logP calculation the following command will also calculate optional druglikeness properties such as molecular weight number of hydrogen bond donors and acceptors number of rotatable bonds and number of rings Results are
7. all Dir throughout the rest of this manual 3 Environment variable configuration In order to execute XLOGP3 from any other folder or directory we strongly recommend you to add the XLOGP3 executable and installation path to your system environment variables a For UNIX Linux systems x86 x86_64 Linux If you are using a CSH or TCSH please add the following contents to the file cshre under your home directory setenv XLOGP3_HOME XLOGP3 Insiall Dir set path path XLOGP3_HOME bin If you are using a BASH please add the following contents to the file bashre or bash_profile under your home directory Note there is no blank around export XLOGP3_HOME XLOGP3 Insiall Dir export PATH PATH XLOGP3_HOME bin If you are using other shells or have problem with installation please contact to your system administrator for help b For Microsoft Windows Platforms 98 2000 2003 XP If you are using Windows 98 platform please add the following contents to the file Autoexec bat under your system installation path typically in CH set XLOGP3_HOME LOGP3 I nstall Dir set PATH PATH XLOGP3 Install Dir bin If you are using 32 bit platform Windows 2000 2003 XP open the user variables dialog via Control Panel gt Performance and Maintenance gt System gt Advanced gt Environment Variables Create a new variable of XLOGP3_HOME set its value as XLOGP3 Install Dir then add XLOGP3 Install Dir bin to the user variable PATH if not
8. for the fast calculation of logP Its predecessor XLOGP and XLOGP2 ref 1 and 2 which are atom additive methods with well defined correction factors have already gained their popularity in this field for their applicability and fair accuracy As the latest release of this series XLOGP3 has implemented an optimized atom typing scheme and is calibrated on a much larger training set More importantly based on the assumption that compounds with similar structures have similar properties XLOGP3 introduces a new strategy by predicting the logP value of a query compound based on the known logP value of a structural analog which is illustrated in Figure 1 This new strategy improves the accuracy of XLOGP3 remarkably It also provides users the possibility of utilizing their in house logP data For more detailed information on XLOGP3 please refer to ref 3 Query logPexp 0 30 onz e 0 085 0 800 Search N V O logPaic 0 29 Geh e logPexp 0 11 Figure 1 The basic calculation procedure of XLOGP3 The following two tables summarize the results of a comparison of XLOGP3 and some other popular logP methods The first test set consists of 406 FDA approved drug molecules 1 Latest revision Dec 2007 XLOGP3 User Manual while the second one consists of 219 oligo peptides Table 1 Results of Some logP Methods on 406 FDA Approved Small Molecule Drugs Models ECH RMSE MUE XLOGP3 0 872 0 72 0 51 XLOGP3
9. ilarity index to given molecule that found in knowledge set is still below 0 50 it will be calculated with pure atom additive model i e XLOGP3 AA Without v the output will be the simplest 8 Latest revision Dec 2007 XLOGP3 User Manual 3 6 Warning and Error Messages All the warning and error messages will be logged to a file named xlogp3 log and also written to screen simultaneously We recommend XLOGP3 users to forward this file to us when problems are encountered with using XLOGP3 Table 3 lists some of the general warning and error messages Table 3 Common Warning and Error Messages of XLOGP3 Warning or Error Message Description Ooops syntax error The general synopsis for using XLOGP3 is error See Section 3 1 for detail Unsupported format X Format X is not supported The only supported formats are MOL2 SDF RDF MOL and MDL and MOL2 and SDF are recommended Unable to open file X Unable to read file X It is normally because the file does not exist or the path provided is not correct Unable to find file matches pattern X Unable to find file matches pattern X See Section 3 4 for detail No TTDB found or supplied XLOGP3 works in XLOGP3 AA mode This may be because the default knowledge set default TTDB is missing or the environment variables settings are not correctly configured See Section 2 2 for detail Missing parameter for ATOM X The type of a
10. ion marks is necessary they avoid the automatic expansion of wildcard by a UNIX Linux shell or Windows DOS command prompt XLOGP3 regards all the characters between as a single parameter and expand it internally if it is wildcard contained 3 5 Program Outputs The verbose output with y parameter of XLOGP3 is like the following Optional Druglikeness Properties of MOL HEascoo5s54 Molecular Weight 132 1 No of Hydrogen Bond Donors 3 No of Hydrogen Bond Acceptors No of Rotatable Bonds No of Nitrogen and Oxygen Atoms No of Rings OO o Dm Gu XLOGP3 of MOL HEaScoOOS5Ss4 2 92 with Similarity Index to Reference 1 00 Contribution from Reference s Experimental LogP 2 92 Contribution from Reference s Calculated LogP 4 05 Contribution from Each Atom C 2 X X 0 760 N am h 0 272 C 3 2h X pi 0 264 0 2 C 0 641 0 3 h pi 0 007 2 X X 0 760 N 3 2h 0 730 C 3 2h X pi 0 264 9 0 2 C 0 641 Contribution from Amino Acid Correction 2 280 C Jann bb GO PA ta Figure 3 An Example of output of XLOGP3 Figure 3 lists the full output of one example molecule including molecular name optional druglikeness properties final calculated logP similarity index to reference molecule and individual contribution A similarity index cutoff 0 50 is currently applied in XLOGP3 for finding an appropriate reference as starting point If the structural analog with the highest sim
11. l TC shell or B shell on UNIX Linux systems or at a Windows or DOS command prompt The following hardware platforms and operating systems are supported lt x86 platforms 32 bit or 64 bit running Linux kernel 2 4 or above x86 platforms running Microsoft Windows 98 2000 2003 XP 2 2 Installation The XLOGP3 program is written in C and has been tested on UNIX Linux and Windows platforms It is provided as executable binary codes for each supported platform To install the command line version of XLOGP3 please follow the instructions below 1 Download the program package via the web server of Computational Chemical Biology Group CCBG at http www sioc ccbg ac cn software xlogp3 Please find the appropriate executable for your own platform Platform Executable name UNIX Linux x86 xlogp3 Inx x86 UNIX Linux x86_64 xlogp3 Inx x86_64 Microsoft Windows xlogp3 win32 exe 2 Copy the downloaded package to a directory where XLOGP3 will be installed and uncompress it A subdirectory named xlogp3 will be created i e the installation path of XLOGP3 It contains the following folders 7 bin contains executable file of XLOGP3 7 manual contains user manual of XLOGP3 7 example contains example files of XLOGP3 7 parameter contains default parameter files of XLOGP3 For the sake of convenience the installation path of XLOGP3 will be referred to as 3 Latest revision Dec 2007 XLOGP3 User Manual XLOGP3 Inst
12. n Li and Renxiao Wang Computation of Octanol Water Partition Coefficients by Guiding an Additive Model with Knowledge J Chem Inf Model 2007 47 in press XLOGP3 13 Latest revision Dec 2007
13. r data sets into the format accepted by XLOGP3 please execute xlogp3 m inputMoleFile outTTDB nameLogpFile This command will process all the molecules in inputMoleFile into a knowledge set named outTTDB an extension of TTDB is recommended e g yourOwn TTDB Parameter nameLogpFile is an index file containing the name and experimental logP of molecule It has the following format Name_of_Molecule_1 Experimental_logP_of_Molecule_1 Name_of_Molecule_2 Experimental_logP_of_Molecule_2 Molecular name must correspond to experimental logP strictly because XLOGP3 will use molecular name as index for experimental logP value Note molecular names should contain no blank Some compounds may be skipped in the preparation step see Table 3 for detail Wildcard is also supported The following command regards all the MOL2 files under yourDIR subdirectory as user data sets and tries to process them into outTTDB 10 Latest revision Dec 2007 XLOGP3 User Manual xlogp3 m yourDIR mol2 outTTDB nameLogpFile 4 2 Supply Additional Knowledge Sets Once a knowledge set is ready for use one may supply it as a parameter as following xlogp3 inputMoleFile outputResultFile yourTTDB Or in a simpler form one may put a copy under parameter subdirecoty then execute with more brief command xlogp3 inputMoleFile outputResultFile Actually all the files under parameter subdirectory with the extension of TTDB will be regarded by XLOGP3
14. tom X is not defined in XLOGP3 we make a guess on its coefficient Unable to construct TT for X skipped Unable to construct Topological Torsion TT descriptor for molecule X it will be skipped when building user knowledge set A TT descriptor requires at least four consecutive non hydrogen atoms Unable to get experimental logP value for X skipped Unable to get the experimental logP value for molecule X it will be skipped when building user knowledge set See Section 4 1 for detail 9 Latest revision Dec 2007 XLOGP3 User Manual 4 ON ADDITIONAL KNOWLEDGE SET Some researchers may maintain their in house collections of logP data For understandable reasons such data are not always available to the public Conventional additive methods are normally provided to users as is and lack the ability of utilizing users in house data We provide auxiliary tools in the XLOGP3 package so that the users may process their own data sets into the format accepted by XLOGP3 and supply them as the knowledge set used by XLOGP3 The importance of this feature should not be underestimated since in house logP data are perhaps many times more than publicly available data We have already provided a default knowledge set i e default TTDB under parameter subdirectory It contains all the compounds in the training set and two test sets of XLOGP3 9000 in total 4 1 Knowledge Set Preparation In order to process use
15. urrent working directory to monitor the warning and error messages of XLOGP3 detailed information can be found in Section 3 6 3 2 Screen a Compound Library In practice user may want to extract certain compounds from a large library for further study according to some restrictions such as Lipinski s rule of five XLOGP3 provides user the filtering tool to screen a compound library using user adjustable rules of the druglikeness properties Just execute 5 Latest revision Dec 2007 XLOGP3 User Manual xlogp3 s inputMoleFile outMoleFile ruleFile All parameters are indispensable Parameter s tells program to perform screen function parameter inputMoleFile is the input filename of compound libraries to be screened All compounds that satisfy the rules that defined in the file ruleFile will be written to a outMoleFile There is an example of ruleFile named default rule under example subdirectory in the installation path of XLOGP3 shown in Figure 2 RANGE OF ACCEPTED MOLECULAR WEIGHT MOLECULAR_WEIGHT o 500 RANGE OF ACCEPTED NO OF HYDROGEN BOND DONOR NUMBER_HB_DONOR o 5 SH H RANGE OF ACCEPTED NO OF HYDROGEN BOND ACCEPTOR NUMBER_HB_ACCEPTOR O0 10 Ba 2 RANGE OF ACCEPTED NO OF TOTAL NITROGEN AND OXYGEN ATOM NUMBER DD ATOM o 15 w 2 RANGE OF PARTITION COEFFICIENT LOGP 2 5 RANGE OF ACCEPTED NO OF ROTATABLE BOND NUMBER_ROTOR 0 10 Ba OH w SH RANGE OF ACCEPTED NO OF RING NUMBER NUMBER_R
16. yl or nitro group sp3 hybridized oxygen atom in hydroxyl group sp2 nitrogen atom in an aromatic ring sp1 nitrogen atom in cyano group lt Rotatable Bond must satisfy a single bond b not a ring bond c not a terminal bond except that connected to OH d not connected to CH3 CX3 X halogen atom C N NH gt NH NO gt PO CO SO3 t Butyl e count only once if a triple bond has two rotatable bonds 12 Latest revision Dec 2007 XLOGP3 User Manual CONTACT INFORMATION You are welcome to post your questions or any comments on XLOGP3 on an on line discussion forum at http www sioc ccbg ac cn forum Or you may contact us at the following address Prof Renxiao Wang State Key Lab of Bioorganic and Natural Products Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Road Shanghai 200032 China P R E mail wangrx mail sioc ac cn REFERENCES Users are required to cite the usage of XLOGP3 XLOGP2 or XLOGP in any resulting publication by making reference to the publications below 1 Wang R Fu Y Lai L A New Atom Additive Method for Calculating Partition Coefficients J Chem Inf Comput Sci 1997 37 615 621 XLOGP 2 Wang R Gao Y Lai L Calculating Partition Coefficient by Atom additive Method Perspect Drug Discov Des 2000 19 47 66 XLOGP2 3 Tiejun Cheng Yuan Zhao Xun Li Fu Lin Yong Xu Xinglong Zhang Ya
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