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Desmond 2.2 Tutorial Workshop

1. Running Prime Click Options gt gt gt gt v Structu re Refinement Options General Seed _ Random 9 Constant Use crystal symmetry Dielectric Internal dielectric 1 00 External dielectric 80 00 Loop refinement Cooperative loop sampling pairs on Select the Serial loop sampling option gt 929 Job maximum a 2 Tu e pro O Distribute subjobs over rocessors Output for single loop feature Maximum number of structures to return Energy cutoff s m Maximum CA movement Select the Unfreeze side chains within gt 222 option and enter 0 0 A so side chains do not move D E Shaw Research Missing Residues amp Side Chains Running Prime loopl loop2 loops loop4 _ 5 Estimated processing time for Default sampling 7 hrs 21 min 1 GHz P4 lick Start gt gt D D E Shaw Research Missing Residues amp Side Chains Running Prime ge e v maestro 9 0 106 Tutorial_project prj proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files m x E 75 fa Y 1 E Ff e AY Maestro Project Edit View Display Tools Applications Workflows Scripts Help Te 1 I y v E ud IPIE 1 iba CS EN ES o H ns E meets 0 71 P C er amp HER
2. UM m NL Chains Molecules Entries Select Atoms 359 15797 Entries 1 4 Res 1115 Chn l Mol 119 Chg 23 Jobs 0 0 4 1504 A Ase SSaSEEILAACISFVLAWFEEGEETITAFVEPFiganmamd M 18UJM A VWC ALK EPENGKVYRADRKSVORIKARDIVPGD IVEVAVGDKVPADIKILS IKSTTLRVDQS IL TGESVSVIKHTEPVPDPRA isut A K IGHFNDPVHGGSWIRGAI 1 7 2 FISU A mmm 4 1504 A KPIRSGOFDGLVELATICALCNDSSLDFNETKGVYEKVGEATETALTTLVEKMNVFNTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCS 4 1504 A PAKSSRAAVGNKMFVKGAPEGVIDRCNYVRVGTTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGM Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Membrane Systems Setting up membrane systems Click the Set Up Membrane button S one i Predefined SPC Custom Browse Tic m n mr Set Iln Membrane Select POPC as the membrane gt gt gt gt aes oec amo model L Cusom Browse Transmembrane atoms ASL optional Click the Select button Place Automatically Place on Prealigned Structure v Adjust membrane position Save Membrane Position to Selected Entries Load Membrane Position from Selected Entry OK Cancel Help D E Shaw Research Membrane Systems Add Subtract Intersect Update Markers Atoms matching Ej Setting up membrane systems PDB B te
3. I 1I CI 1 1 ted T I 1I Vz 150483 A MEAAHSKSTEEC LAY FGVSETTGLTPDOVERHLEKY GHNELPAEEGK us 4r es u vj oe ehh 4 Build an all atom model based on the alignment from the previous a rue Build Structure Write Click Options Include ligand Omit structural discontinuities 1sud missing loop A C Insertions template gaps of more than lsud missing loop A n Lsu4 missing loop_A x L _ Template junctions 20 90066 O Deletions query gaps e Limo dg A cio RIPE oa Select the Retain rotamers for i e dues conserved residues and Optimize side chains options Click OK d to Project Table Comparative Modeling Edit Build Alignment Structure Input Find Sequence Homologs Fald Recognition Threading Commands middle xy rotate ctrl middle z rotate right xy translate right d Close f Help D E Shaw Research Missing Residues amp Side Chains Running Prime Tutorial project prj proj desres Desmond DropBox Desmo nd_Tutorial_2 2 T utortal_2 2_work Desmond_job_files BEE 0 Maesro Prec Edt View Display Tools pl ay pom a Cris Tae Se d gis gt e e HH VER o XH On 3 File Edit Display Step 3 he
4. m Adjusting the conformation of the mutant z hdd maestro 9 0 108 Academic Use Only proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files Maestro Project Edit View Display Tools Applications Workflows Scripts Help G 1 EH TE H 9 0 H S 2 alin a 5 HOW ty 7 H ts O CJ Vi lL P AUS A 1 os a hh wr Atoms 98 98 Entries 2 3 Res 3 Chn 2 Mol2 Chg 8 Jobs 0 0 Commands jmiddle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research m Other types of mutations e Protein residue mutation Compute the difference in free energy for a ligand bound to a protein versus the same ligand bound to a mutated form of the same receptor with amino acid residue mutations applied to the protein Compute the difference in free energy for a protein versus a mutated protein without a ligand e Ring atom mutation replace one atom with another in a ring structure Absolute or total free energy calculation Compute absolute solvation free energy and absolute binding free energy by annihilating a whole solute or ligand molecule DE Shaw Research Free Energy Perturbation Vis
5. 5 A 0 ZF amp A 1 A A 4 al A ASN 43 6 CA gt THE GEOMETRY OF THE REACTIVE SITE AND OF THE PEPTIDE GROUPS IN TRYPSIN TRYPSINOGEN AND ITS COMPLEXES WITH INHIBITORS middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Jl ME us ETT3 we GY IT apy ee rT Maestro Project Edit View Display Tools Applications Workflows Scripts Help A w hae DO OLLIE T L met ev 22 ER Cw b N er H H wy 0 x uy H Ti c Be E E Cc T Y o ot eet XYZ v 4m o o 4 a gt 7 4 2 S amp SFO ada A ASN 43 C CA THE GEOMETRY OF THE REACTIVE SITE AND OF THE PEPTIDE GROUPS IN TRYPSIN TRYPSINOGEN AND ITS COMPLEXES WITH INHIBITORS middlezxy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Prepare for simulation Change view D E Shaw Research Mae Projec dit D ay JIS orkflows Scripts Help prm m 1 A Job prefix iprepwizard 8 nooooq P 1 oe A i 0 1 A gt EI Q C3 20 TH E a e 49 CO WW oS PDB Diffraction data Browse RA e 7
6. B Atoms 0 15435 Entries 1 6 Res 994 Chn l Moll Chg 27 Jobs 0 0 m Builda A IEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEQFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILIANA 4 b ii JGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRAVNODKK ub A ALFSGTNIAAGKALGIVATTGVSTEIGKIRDOMAATEQDKTPLOOKLDEFGEQLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIP 67 3LPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKNDKPIRSGOFDGLV _ Bur A ATICALCNDSSLDFNETKGVYEKVGEATETALTTLVEKMNVFNTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCSPAKSSRAAVGNKMFV 6 3 TA 3APEGVIDRCNYVRVGTTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGMLDPPRKEVMGSIOLCRDA Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research eb o f AAI e AII S A S Running Prime Table Select Entry Property Group ePlayer RA N ex Be Ee i fe gt t 28200 8 28238 5 i Dele 2D structure height p 200 Entries 6 total 6 sh own 1 selected 1 included Groups 0 total 0 selected Missing Residues amp Side Chains The Prime energy of the structure is lower with the refined loop than with the initial loop The current state of gt gt gt
7. 9 C amp mR10 HH mii 30 A amp THRII HGL initial gt Ba i A TYR 21 HH Initial gt 12 ATYR23 HH Initial HE 13 C ATHR32 HGI Initial lt gt 20980 A TYR 35 HH Initial gt 15 r ASER47 HG Initial lli Pick to locate species Close Help D E Shaw Research Simulation Steps Refine the protein structure Protein Preparation Wizard om VEL x Subject the protein to constrained prm fi 1 Display hydrogens None Polar only All E and analyze structure Ww Assign bond orders Add hydrogens Treat metals Selenomethionines Treat disulfides W Find overlaps Delete waters 5 A Fill loops W Cap termini e e lick Minim IC IZ Preprocess Analyze Only Chains waters and het groups requires Glide license a e Preferred method is using Desmond s own minimization protocol Generate Het States Metal mode Delete Selected H bond assignment er Exhaustive samplin Optimize P 3 iw Sample water orientations Interactive Optimizer Click the Minimize button Reset Close Help DE Simulation Steps Generate a solvated system 7 0 107 test prj home istvan pufer Desmond_2 2_Tatornal EK Maestro Project Edit View Display Tools ES Applications lorkflows Scripts Help mide HH OOOO de 0 ES ConfGen
8. ILL E RA e CEH a B Search for or import sequence homologs then select an appropriate w top of the panel 8 OA 77 z x j s 1 lt r l T mH il 5 i Search import Aliam Structures Options 0 9 J kb Ba 96 7 5 Query family name Find Family d tit 0 a Bn Comparative Modeling Next gt Click Next amp click Next again ES Comparative Modeling E dit Build Alignment Structure Atoms 120 7752 Entries 1 4 Res 1109 Chn 1 Mol 117 Chg Input Find Sequence Homalogs See Fold 4 1504 A MEAAHSKSTEECLAYFGVSETTGLT 4 1504 A Recognition VGVWOERNAENAIEALKEYEPEMGK Threading TNIAAGKALGIVATTGVSTEIGKIR 4 1504 A ITTCLALGTRRMAKKNAIVRSLPSV a 1s0a A 6 878 4 1504 A VIDRCNYVRVGTTRVPMTGPVKEKI Commands middle xy rotate ctrl middle z rotate right xy translate right click on ato D E Shaw Research Missing Residues amp Side Chains Proteins with missing residues ini Prime Tutorial project prj proj desres Desmond DropBox Desmond Tutorial 2 2 T utorial_2 2_work Desmond_job_files tig 7 EXE o x 5 7 Maestro Project Edit View Display Tools Applications Workflows Scripts Help pn Z A CCG x i Ad ty die A DO O O OC di a File Edit Display Step MI X cH IW dq d amp amp i i fi I 1I I AU 1 18
9. 5 Job prefix Iprepwizard Display hydrogens None Polar only All u 1 L Preprocess and analyze structure Em m Iv Assign bond orders v Add hydrogens Treat metals Selenomethionines Ww Treatdisulfides v Find overlaps dius X Delete waters 5 D Fill loops v Cap termini Analyze Only a ya H planc eL T 4 r Chains waters and het groups La 2 W Fiton select 0 selected Pick ar Wi ge Q ll Eup olg xyz ER is lL v 3 CA 995 lt gt lt gt ES CA 996 3 NA 997 d qd Tus lt Metal mode Delete Selected lt q T Delete the selected ra ze B H bond assignment 4 y Exhaustive samplin Optimize p W Sample water orientations Interactive Optimizer I mpref minimization to RMSD A 0 30 2 amp Atoms 7791 7791 Entries 1 1 Res 1114 Chn 1 Mol Je _ Hyarogens Force field 71 H P4 Commands Displaying state jmiddle xy rotate ctrl middle z rotate right xy translate righ Reser Close Help Membrane Systems Select Workflows gt Protein Preparation Wizard Enter Isu4 in the PDB field and click Import Check options for preprocessing as shown do not delete crystal waters Click Preprocess
10. Viparr Simulation Steps Configure simulation parameters maestro 9 0 107 test pr fomefstvan bufferID Maestro Project Edit View Display Tools Applications Workflows Scripts Help OQ Bune Minimization eT EE ee Tn Molecular Dynamics Replica Exchange FEP Ligand Functional Group Mutation by FEP Protein Residue Mutation by FEF Ring Atom Mutation by FEF Total Free Energy by FEP simulation Quality Analysis Simulation GombiGlide M GonfGen Epik Glide Impact Jaguar Liaison LigPrep MacroModel MGPRO Phase Prime Primex QikProp OSite SiteMap Strike AG luster I H 1 1 C H aa H Y 1 GE Ee EE zu 2222 Atoms 13686 14010 Entries 1 4 Res 4419 Chn 2 Mol 4391 Chg 0 Jobs 0 0 middle xy rotate ctri middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu gt gt E vv D E Shaw Research Configure simulation parameters Select Load from gt gt gt Tf The system contains 14022 atoms and was set up for nor FEP simulations Workspace imulation time ns Enter 0 12 ns as the 2 23222 sies cased simulation time Ensemble class NPT Temperature K 3000 Pressure har 1013255 Select the Relax model gt gt gt gt Relax model system before simulat
11. iv bi es C iy wy o Wi 7 H bu amp L1 Li vl L qi fod ye ur v R e m ub KA vw eh f 90 oe XYZ v O a J cL Ww k d Ch NL H Atoms 40 40 Entries 1 3 Res 2 Chn 1 Mol 1 Chg 3 Jobs 0 0 Commands j middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Atom Properties Select the Grow option gt D Fragmenti Diverse Fragments Select the Pick option and choose Bonds e an Select Diverse Fragments from Fragments son smn ens Sanne protonated morphlinomethyl 2 morpholinoethy i 2 Booo Joining Geometry anti D E Shaw Research Free Energy Perturbation reating a custom fragment group m maestro 9 0 108 Academic Use Only proj desres Desmond DropBox Desmo nd Tutorial 2 2 Tutorial 2 2 work Desmond job files Maestro Project Edit View Display Tools Applications Workflows Scripts Help 4 j 8 9 0 H P EP ne ee TAS v ad amp J as e H wy o XH H bn A L Ney VJ Se a 23 Ps kd T ws m Y 7 KA M p vr e n Atoms 40 40 Entries 1 3 Res 2 Chn 1 Mo
12. 1 NASN24 No Flip BEI AGN31 MWorip lt gt a c AANA NeHp lt lt a r Aasnaa NoFlip lt gt s C asp3 Charged lt gt Im H xGLU7 Charged gt lt i al A GLU 49 Lets Residue sta 7 IT m ATYR21 ATYR23 HH ATHR32 HGl 14 ATYR35 HH Initial lt gt 15 r ASER47 HG Initial le l Initial Initial Initial Initial Initial e Atoms 752 1082 Entries 1 3 Res 120 Chn 1 Mol 61 Chg 7 Jobs 0 0 middle xy rotate ctrl middie z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Pick to locate species Close DE shaw Simulation Steps Prepare for simulation Prepare protein Oe eo Interactive H bond Network Optimizer D A Analysis Analyze Network Include current orientations Only analyze Workspace selection Use crystal symmetry View all species 76 species total t View cluster EJ sn gt 30 clusters total D Click Optimize All to re optimize the gt 22 gt yd oge bo d 8 etwo Ee A 2 amp GN31 gt 3 C AASN43 Nofip a AASN44 Norip 5 T wasps Charged lt gt 66 rC 7 Charged lt gt 7 Gua9 charged ajm MASPSO Neutal2
13. Prime E Total Free Energy by FEP PrimeX simulation Quality Analysis QikProp E asite nc U A SiteMap CA 0 Strike AGluster Monitor Jobs 1 Atoms 49 49 Entries 1 1 Res 1 Chn 1 Mol 1 Chg 5 Jobs 0 0 Commands Pick atom in molecule to delete D E Shaw Research Generating a Desmond FEP file EX RE Model system Load from Workspace Load The system is not specified Simulation FEF type Mutation Total free energy Soft core parameter 05 Number of windows 12 if Setlambda values automatically Window index Iv D Ww 1 Iv 2 lw 3 wv 4 v 5 Select the windows that should gt gt gt gt vdwE lambda 0 0 0 1185140 1897780 247414 be included in the simulation ChawgeAlambda 10 075 05 025 00 00 00 Charge lambda 00 00 00 00 oo 00 po BondingA lambda 10 10 10 10 10 0857142071 BondingB lambda 0 0 0 1428570 2857140 428571 0 5714280 714285 0 85 VdwA lambda 1 0 0645 07 Select All Windows Deselect All Windows Simulation time ns total 12 elapsed 0 Recording interval ps energy 12 trajectory 4 8 i Ensemble class NPT Temperature K 300 0 Pressure bar 1 01325 w Relax model system before simulation Relaxation protocol Use default protocol Browse Advanced Options Desmond Developed by D E Shaw Research Click Write P Start Read Reset Close Help D E Shaw
14. we H T _ EE j TA hp haga X Elh AAAET c3 c L3 L3 amp amp Te am f ee E 7 1 1 eL IN 0 og aa A T I I1I og gd l 1 1 E 1SU4 A ERE BAVE EREBE BREESE i zd b al 4d LJ Tm A Build an all atom model based on the alignment from the previous Build Structure gt Step Write Include ligands and cofactors Omit structural discontinuities j ex elo x 1su4 missing loop A C Insertions template gaps of more than e lsu missing loop A C _ 020 4h 4 1sud missing loop A xl _ Template junctions 46 _ Deletions query gaps as Li m 2 Co 8 Log file Loading template templatel_A Initial model constructed Now refining initial model Preprocessing using PrepWizard lt Back Add to Project Table Comparative Modeling Edit Build E Alignment Structure Input Find SS Atoms 120 7752 Entries ljd Res 1109 Chn 1 Sequence Homologs M ET MOOR d Fald 1 1504 A Threading H cnamlion middle xy rotate ctrl middle z rotate right xy translate righ Missing Residues amp Side Chains Proteins with missing residues Click Build Results appear as the structure is built Click Add to Project Table Click Close D E Shaw Research
15. Importing membrane placement from OPM D E Shaw Research Membrane Systems Generating force field parameters with Viparr Assign alternative force field parameters with 7 e Viparr is a Python script that reads cms or mae files e Refers to a template database to assign force field parameters Matches residues to templates using atomic numbers amp bond structure Built in force fields include latest versions of Amber CHARMM and OPLS AA for fixed charge model and p f polarizable force field e Wipes out existing io structure in the cms input file Does not alter atom or residue ordering when creating the output file Recommended perform post processing on cms with Viparr Invoke from command line SCHROD INGHIEY run FROM desmond viparr py help D E Shaw Research Force Fields with Viparr Generating force field parameters with Viparr Can specify multiple force fields e Example o vipa fe f charmm27 f 9 85 1 8114 deSi eme out cms Combine components of two or more force fields e All matching force fields are applied Conflicting parameters first force field in command line invocation takes precedence Viparr aborts if a bond exists between two residues that are not matched by the same force field or if force fields have inconsistent van der Waals combining rules D E Shaw Research Force Fields with Viparr Generating fo
16. Running Prime bd Maestro 9 0 106 Tutorial project prj projjdesres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files Maestro Project Edit View Display Tools Applications Workflows Scripts Help 1 1 H Q 0 H DENEN NUES GSP R AT a 05 l 2 rh DD A d 7 Tx Bs ESE HO TH N o XH eb H bn A O VJ i 3 ll al lt Ls 1 HH H c 0 Y m A 4 b 3 8 Fo n Lu B A BA FP Atoms 123 30939 Entries S 1 4 Res 1114 Chn 2 Mol 235 Chg 73 Jobs 0 0 MEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEOFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILIANAI VGVWOERNAENAIEALKEYEPEMGKVYRVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRAVNODKKNMLFSG TNIAAGKALGIVATTGVSTEIGKIRDOMAATEODKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIPEGLPAV l 4 1504 A T 18UJ A ITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKNDKPIRSGOFDGLVELATIC T 18UJ A ALCNDSSLDFNETKGVYEKVGEATETALTTLVEKMNVFNTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCSPAKSSRAAVGNKMFVKGAPEG 2 J 15U43 A VIDRCNYVRVGTTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGMLDPPRKEVMGSIQLCRDAGIRVIM Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research E Prime b
17. frame 0 m prolO fit proO weight mass prol0 move m rms prolO fit proO D E Shaw Research Working with VMD Atom selections in VMD e Extracting positions and velocities from frames expensive Get the x y z coordinates for atoms in watl watl get x watl get y watl get z NK x Get the z component of the velocity vz watl get vz e Extracting positions and velocities with vmdnumpy Return reference to coordinates vmdnumpy positions molid 1 frame 1 Return reference to velocities vmdnumpy velocities molid 1 frame 1 D E Shaw Research Working with VMD Atom selections in VMD Extracting a subset of coordinates for a selection Return all positions in top molecule s current frame pos vmdnumpy positions Return index of all CA atoms inds ca get index Return M x 3 array where M len ca ca pos pos inds D E Shaw Research Working with VMD Functions from VMD built in molecule module new name molid of newly created molecule listall list of available molia values numatoms m number of atoms in molecule m numframes m number of frames snapshots in molecule m get top molid of top molecule if none set top make molecule m the top molecule get frame get current frame for molecule m set frame m frame Set current frame for molecule m to frame get
18. 0 M The solute and gt gt boundary box Atoms 752 1082 0 5 118 120 Chn 1 61 Chg 7 0 middle xy rotate ctri middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Z D E Shaw Research Simulation Steps Neutralize the system lick the lons tab 22 Exclude ion and salt placement within 7 0 A of RR ces Enter 0 5 M salt gt gt gt Salt 0 15 Salt positive ion Na Salt negative ion Cl concentration Click Start gt gt gt D E Shaw Simulation Steps Generate a solvated system a nm nm mp mm m ES iiu 9 med Maestro Project Edit View Display Tools Applications Workflows Scripts Help 1 t H 9 0 H N SN s Aq gt gt n 5 HoH o XH 22 H En A ER Y NJ he XA EE RA ef t lc T ot ex p XYZ Yo 4 o o ih d ow a S MN a rw 1 Q A d A WW QR H Atoms 13686 14010 Entries 1 4 Res 4419 Chn 2 Mol 4391 Chg 0 Jobs 0 0 middle xy rotate ctri middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Assign force field parameters Maestro automatically assigns the latest OPLS AA force field parameters to the system Desmond offers additional force fields that can be applied with
19. RA Aj MES 4 w A 0 wt S ww n Atoms 49 49 Entries 1 2 Res 1 Chn 1 Mol 1 Chg 5 Jobs 0 0 Commands i middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research reating a custom fragment group Define Plan Step 1 Display the ligand and its receptor if any in the Workspace Pick the attachment bond to define the core and the step 2 substitution group Pick the attachment bond Step 3 Select fragments that will replace the substitution group Fragment library 9 items litem selected Y sesame No Fragment Name View Reset Select the methyl fragment as gt gt gt gt MN the base of the butyl substitution group amino r pee ammonio Click View chloro hydro E a 3 4 5 6 carboxy lj fluaro 9 8 9 9 E Desmond Develo by D E Shaw Research Start Write Reset Close Help DE Shaw Research Free Energy Perturbation reating a custom fragment group 0 20 108 Use Only jproj desres Desmond DropBox Desmond Tutorial 2 2 T utorial 2 2 work Desmond job file rojed Edit View Display Tools Applications Workflows Scripts Help 1 5 H 0 H pU S eh
20. File gt Save Coordinates Add force field parameters and constraints with parr and the build_constraints script D E Shaw Research Building Systems with VMD Preparing molecular systems with VMD ZI 7 85 1 e wu X4 Pp Ray 7 a 7 Lox NL a a al Pal Cl P a al Pal P al Pl Cal P Pal a A PB P LALA LALA P P a P a al P al P P I a al I I Pl I P al Pal LA SALA ALLL ALA LALA a P P C P I P a a I P a a LALA P P P P P a P P P a a LALA P al P al P a a a a Pl P al Pal LA LAA Building Systems with Preparing molecular p with VMD ples TAD FE Molecule Atoms 7 27 AutoPSF Options otep 1 Input and Output Files Molecule 1 4ptipab e 1 4ptipab e Output basename 41 autopst Topology files pro j dezgrez raot Linux xBb Bd vumd l1 8 ab e Delete inorganic Builder Membrane Builder Merge Structures Molefacture Mutate Re sidue Nanotube Bui Ider otep 2 selections ta include in PSF PDB Par meterization Taol J Everything E Protein Nucleic Acid _ Other Guess and split chains using current selections Step 3 segments Identified Mame Length Index Range Hter Cher Type Add a new chain Edit chain Fi Delete chain Create chains otep 4 Patches Patch Segid Eesid SegidtResid F1 5 amp dd patch DISU P1 14d P1 38 DISU P
21. SDIVEVAVCDKVPADIRILSIKSTTLAVDOSTLTGESVSVIKHTEPVPDPRA EIGKIRDOMAATEO Wey 11 IGHFNDPVHGGSWIRGAT YY Residue Position AIVREMWENBMLGCTSVICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKND KGVYEKVGEATETALTTLVEKMNVFNTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCS E ntry GTTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGM Constant Color mme POT eT IgA YTS Ignore or aron sporcenter right click on atom bond and hold menu D E Shaw Research Membrane Systems Setting up membrane systems X Solvation lons Adjust the oca scope U FE for transformations Membrane model Predefined 0PC 300K CC Custom Browse Transmembrane atoms ASL optional Seed Place Automatically Place on Prealigned Structure Check the Adjust membrane gt D DD znenane postion Save Membrane Position to Selected Entries position button in the Set Up Membrane Load Membrane Postion fom Selected Enty window Cancel Help Translate and rotate the membrane model in the Workspace relative to the protein structure Membrane Systems D E Shaw Research Setting up membrane systems hd maestro 9 0 108 proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files Maestro Project Edit View Display Tools Applications Workflows Scripts Help we gt T oS otek ete AL EHE 5 UR a Y Atoms 359 15
22. gt the Project Table after loop refinement X ray structure 5 initial loop 6 refined loop D E Shaw Research Running Prime v maestro 9 0 106 Tutorial_project prj proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files Maestro Project Edit View Display Tools Applications Workflows Scripts Help 1 t H 9 0 H a a Ae P AKER 2 Lg HOH N oh oe a E Ly Ve EFESE HH H I Nap NS LP ge re etined ow i A LYS 35 C CA CRYSTAL STRUCTURE OF CALCIUM ATPASE WITH TWO BOUND CALCIUM IONS 1 1504 A MEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEOFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILIANAI 5 Buil A MEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEOFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILIANAI 6 Buil A MEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEOFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILIANAI I ISUTA VGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRAVNODKKN 5 Buil A VGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRAVNODKKN 6 Bui 1A VGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRAVNODKKN Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right c
23. skip 10 waitfor 1 D E Shaw Research Working with VMD Organization in VMD e VMD data is organized into Mo ecu es which represent entire molecular systems and associated snapshots e Molecules are assigned integer keys molia e One molecule is tagged as the top Each molecule has a fixed number of atoms e Atoms are assigned attributes e g name type mass charge Snapshots are referred to as 6 gt Each frame holds one set of coordinates for each atom and unit cell dimensions for the frame e Velocities can be stored if specified by trajectory file D E Shaw Research Working with VMD Atom selections in VMD Consist of all the atoms in a particular molecule and frame that satisfy a predicate or set of conditions ould be different for different frames e Scripting interface uses atom selection to specify a predicate for an atom selection object Atom selection objects created in VMD Python with atomse1 module Import the atomsel type from atomsel import atomsel Create a selection of atoms in the top molecule for the current frame all atomsel D E Shaw Research Working with VMD Atom selections in VMD Select atoms named CA in top molecule in current frame ca atomsel selection name CA Select protein atoms in frame 10 of top molecule prol0 atomsel protein frame 10 Select waters near the protein from molecules O and 1 wat0 atomsel water and
24. 9 o H pu Ze CX AP ou ue 6 p 7 C f pns p Y 8 X 3 ey 1 M 2 Atoms 13587 14476 Entries 1 1 Res 4583 Chn 2 Mol 4530 Chg 0 Jobs 0 3 Commands j middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Visualization and Analysis DE Shaw Research Visualization and analysis using Maestro Simulation Quality Analysis Select Applications gt Desmond gt 222 writs Sem dem P i N H on a s eU A Gl DURER Ae om VA ux A CO CPC IE 4 Simulation Quality Analysis 2 Click Browse and select gt gt gt Job base name lprojjdesres Desmond DropBox Desmond Tutorial 2 2 T aora 22 the energy file Simulation summary Properties or d d b Job name projjdesres Desi Average Std Dev Slope ps 1 esmon JO ene Job progress Normal Total energy kcal mol 38930 67 1 372 0 005 Suan inc ie Potential energy kcal mol 47955 96 53 912 0 014 Degrees of freedom 29418 Temperature K 300 036 1 066 0 001 Click the Analyze button 8 Pressure bar L6 353 75 281 0 096 Volume 3 146904 6 226 754 0 053 Results of analysis appear Close Help 2 Atoms 0 0 Enties 0 0 Res 0 Chn 0 Mol 0 Chg 0 Jobs 0 0 L1 Pd Commands middle xy rotate ctrl middle z rotate right xy translate right click on at
25. A m 5 1 e Epik Minimization m Glide Simulated Annealing 9m X Impact Molecular Dynamics p H 4 97 Replica Exchange s Liaison iR A A SS FEP xvn LigPrep l J 0 Ligand Functional Group Mutation by FEP uw MacroMadel wt es Protein Residue Mutation by FEP 2 MGPRO io Q xyz E E i Phase Ring Atom Mutation by FEF Pd Total Free Energy by FEP 4h 4 Prime zs P lt 4 Primex Simulation Quality Analysis Y P ia Q SiteMap 2 Co VR 3 e QikProp 8 o QSite A 1 Strike o 4 amp AG Iuster gt PHS le Monitor Jobs i 1 rc P Yom be arc y re 27 1 P P LI e Ed Atoms 752 1082 Entries 1 3 Res 120 Chn 1 Mol 61 Chg 7 Jobs 0 0 middlezxy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu C JI iImulation D E Shaw Research 01111 Generate a solvated system solvation lons Set Up Membrane Solvent model None Select SPC as the solvent gt S SD resene E Custom m od e Boundary conditions Box shape Orthorhombic Box size calculation method Buffer Absolute size Distances a 10 0 b 110 0 Angles Box volume 158881 A Calculate Minimize Volume w Show boundary box except truncated octahedr
26. Homologs 4 1sud A MEAAHSKSTEECLAYFGVSETTG JZ 158U1 A MGVWOERNAENATIEALKEYEPEN a 1s04 A NDAAGKADGIVATIGVSTEIGH a 1s01 A ZTTCDALGTRRMAKKNAIVRS a 1s04 A 2000106622 a 1s0a A MIDRCNYVRVGTTRVPMTGPVKE Commands pea rotate ctrl middle z rotate right xy translate right click on Missing Residues amp Side Chains Full sequence of residues appe Click Next D E Shaw Research Proteins with missing residues Running Prime e e Na _ _ _ IRCM 6 9 v maestro 9 0 108 Tutorial project prj proj desres Desmond DropBox Desmond_Tutorial_2 2 Tutorial_2 2_work Desmond_job_files x 0 0 ri m e y Uu ng e Maestro Project Edit View Display Tools Applications Workflows Scripts Help 3S uw i H f 0 H M ar 7 d 4 i gt it H e e uw Tu me v m H bn A L CJ 4 J an E Ae RV Q Sys Bn Structure Prediction TTA XEXEXEFEXEFEREREREKEREKEFEREEFEREREREREREEEFEREFEEERERERFERFEFEREFEFERKEFEEEZT If f E File Edit Display Step z m ate Em DA Ae AA iL e e se C p haga EH IM L3 L3 Bm I llI C ee I I1I gg LT b 1741 71 1 t I 1 40 11 l I EVA li bor og g I T A 15U4 A LAYFGVSETTGLTPDQ
27. J Trajectory Player Select Project Show Table 5 555 eem mm me Table Select Entry Property Group ePlayer 2D structure height H Close j Entries 1 total 1 shown 1 selected 1 included Groups 0 total 0 selected Led w P oq Atoms 0 0 Entries 0 0 Res 0 Chn 0 Mol 0 Chg 0 Jobs 0 0 Commands I middle xy rotate ctrltmiddle z rotate right xy translate right click on atom spot center right click on atom bond and hold Visualization and Analysis In the Project Table click the T button in the Aux column D E Shaw Research Visualization and Trajectory Player Options for frame control e lower quality drawing to speed up play Show simulation box B Show axes Options for display look and feel gt DDD E E E The Trajectory Player will generate m a smooth animation that you can save as a MPEG movie You can take snapshots of the trajectory and save it in Maestro format Visualization and Analysis D E Shaw Research Visualization and analysis using Maestro 0 D Aa a ul a ul i LLL a a i a a ul i a i ll ai a i ai ul i a a li a i a ui a i ai a a a a a i a ul i a a i ai a a a ai a ai a ai a ai a a i ai a i dd dd a ai i ai ui ui a ai a ai a ai a ai a ai ui ai a i ui AA ai uf F x d Maestro Project Edit View Display Tools Applications Workflows Scripts Help H
28. Research learning Maestro Handling missing residues or side chains e Most protein structures in the PDB database have missing residues or side chains with missing atoms Protein Preparation Wizard does not address these issues e Maestro s Prime tool can automatically build a three dimensional model of a complete amino acid sequence e Prime can be fooled into filling in missing residues and side chains in an Incomplete protein structure You need a license for Prime from Schrodinger LLC D E Shaw Research Missing Residues amp Side Chains Running Prime Download the 1 04 structure to Maestro 2 Delete residues 132 136 from the structure by hand and save it as 1 04 _ missing loop pdb 3 Import the modified PDB structure into Maestro Ignore the warning message that refers to the missing residues D E Shaw Research Missing Residues amp Side Chains Running Prime v maestro 9 0 108 Tutorial_project prj proj desres Desmond DropBox Desmond_Tutorial_2 2 Tutorial_2 2_work Desmond_job_files 11111111 Maestro Project Edit View Display Tools Applications Workflows Scripts Help 1 t H PO 77 479g 4 0 1 9 9 H MEN jl 4 A gt gt GE HOH N oH uH A El t EU TEC P d v E K I H H H A A Xo qi 25 v sy T T 4 c 2 xi xX We 3 AS VM 9 amp Atoms 120 7752 Entries 1 4 Res 1109 Chn 1 Mol 117
29. e Edit any pre defined substitution group manually with the Build Edit tools in Maestro e Mutations of more than a few atoms are subject to large uncertainties in the free energy differences computed between different Lambda windows Decompose large mutations into several smaller mutations and run multiple MultiSim FEP simulations D E Shaw Research Free Energy Perturbation reating a custom fragment group Define P Plan Tee Stepl Display the ligand and its receptor if any in the Workspace Pick the attachment bond to define the core and the substitution group Select the Pick the attachment gt gt gt gt gt Dy Pte atactment bond bond 0 pt 0 1 Step3 Select fragments that will replace the substitution group Fragment library 9 items litem selected Step 2 Fragment Name niinus by D E Shaw Research W Reset Close Help DE Shaw Research Free Energy Perturbation reating a custom fragment group E 1 T 1 j z rr bd Maestro 9 0 108 Academic Use Only proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 workDesmond job files l le Maestro Project Edit View Display Tools Applications Workflows Scripts Help 9 t 5 op 1 H oO 2 C d S E EP o x zt CSF 0 Ld ww y Y S J Y ES x ay Wp m i Es X 7 Y i
30. fipt_Desmond_un J Username kolossva Select the host where the Hose Use the subjob host master job should run Bg 1 170 usually localhost Host swdev 64 CPUs subjob 8 Details gt gt Set Job submission parameters gt The system will be domain decomposed as follows x am Y 2 Z B Actually needs 8 CPUs subjob Maximum simultaneous subjabs 0 Click Start gt gt gt gt eee Ee e D E Shaw Research Running Simulations Running Desmond simulations e Run simulations from the command line SSCHRODINGER desmond HOST hostname exec lt demend task P cpu ISI wore in jobnbEmWe cms e where desmond task can be minimize simple minimization mdsim MD simulation vrun trajectory analysis jobname I the name of the job hostname IS the name of the compute host or queue on a cluster cpu specifies the number of CPUs you want each Desmond simulation subjob to use either for quick tests or a power of 2 D E Shaw Research Running Simulations Running Desmond simulations e Advanced issues to consider The Desmond driver tries automatically to optimize configuration parameters turn this off using the noopt argument Automatically generate Desmond configuration settings for efficient force computations with the forceconfig script SSCHRODINGER run FROM desmond forceconfig py lt input cms gt While a Desmond job is running all files for the Job are cont
31. interval ps energy 1 2 trajectory 8 Ensemble class NPT B Temperature K 300 0 Pressure bar 1 01325 Select the Relax model system e Relaxation protocol Use default protocol Browse before simulation option Advanced Options Desmond Developed by D E Shaw Research Click Start s Mu ut Read Write Close Help D E Shaw Research Desmond Simulation Desmond simulation parameters Click Advanced Options Integration Set multiple time step parameters and constraints Ed Molecular Dynamics Advanced Options Integration Ensemble interaction Restraints Output Misc e Ensemble Set thermostat and barostat parameters W Settime steps automatically based on constraint setting RESPA integrator a sl E step fs bonded 2 0 near 2 0 far 6 0 Interaction Set parameters for computing non bonded interactions Constrain WwW Constrain heavy atom hydrogen covalent bonds E 16513111 6 multiple sets of atoms to Shake tolerance 1e 8 Maximum iterations 8 harmonic restraint with a tunable force constant e Output Control output file names and specify how often files are updated during simulation OK Apply Cancel Help e Misc Set miscellaneous parameters including the definition of atom groups
32. or the construction of trajectory files DE Shaw Research Desmond Simulation Running Desmond simulations e Run Desmond simulations by Clicking Start in the Molecular Dynamics window Entering commands at the command line Structure relaxation prepares the system for production quality MD simulation e Maestro s relaxation protocol includes 2 stages of minimization restrained and unrestrained 4 stages of short MD runs with gradually diminishing restraints and increasing temperature D E Shaw Research Running Simulations Running Desmond simulations v EE Model system Load from Workspace The system contains 14022 atoms and was set up for non FEP simulations Simulation Simulation time ns total 727 elapsed 0 ki Recording interval ps energy 12 trajectory 4 8 Ensemble class NPT Temperature K 300 0 Pressure bar 1 01325 w Relax model system before simulation Relaxation protocol Use default protocol Browse Advanced Options Desmond Developed by D E Shaw Research Click Start Start Read Write Reset Close Help D E Shaw Research Running Simulations Running Desmond simulations M Molecular D ynamics Start Outpu Select Append new entries gt gt gt gt to add results to the current project Master job Multiple simulations to run Each simulation will be run as a subjob Enter a name for the Job 46 Name
33. prj home istvan buffer Desmond 2 toria lu ruled 2 mum oS Maestro Project Edit View Display Tools Applications Workflows Scripts Help Job prefix prepwizard Operates on Workspace Gir oy A O O OOOO X HH H H PDE l Diffraction data Browse Display hydrogens None Polar only All r Preprocess and analyze structure ve W Assign bond orders w Add hydrogens Treat metals J Selenomethionines Treat disulfides v Find overlaps Delete waters 5 A T Fill loops W Cap termini cape Preprocess Analyze Only r Chains waters and het groups Ww Fit on select Display only selected Pick Jer Chain Name Residue Name s Ir Metal mode Delete Selected H bond assignment Exhaustive sampling i Sane water orientations Optimize the h a citata Impref minimization Dy clicking Inte Minimize to RMSD A 0 30 Hydrogens only X Force field OPLS2001 Optimize Atoms 751 1081 Entries 1 3 Res 120 Chn 1 Mol 61 Chg 6 Jobs 0 0 selected 1 water middle xy rotate ctri middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Reset Close Help D E Shaw Research simulation Steps Prepare for simulation Prepare protein Click Analyze Network gt gt gt gt L Use crystal sy
34. proj desres Scripts Help 2 Eu Le cy ILC ILS Le Te AAT Minimization simulated Annealing Molecular Dynamics Replica Exchange C C Ligand Functional Group Mutation by FEP TUCCI YE It AUT TI uy T EU ss Ring Atom Mutation by FEP Total Free Energy by FEP simulation Quality Analysis L Q QOO nRav Desmond Tutorial 2 2 Tutorial 2 2 workDesmond job files Applications forkflows zm Hide Ganten bh EPIR Glide Impact Jaguar Liaison LigPrep MacroModel MGPRO Phase Prime Primex QikProp OSite SiteMap Strike AGluster Monitor Jobs Maestro Project Edit View Display Tools LU Clean up ge Fr 5 e Ed a n E T Hrs Atoms 49 49 Entries 1 1 Res 1 Chn 1 Mol 1 Chg 5 Jobs 0 0 Commands Pick atom in molecule to delete D E Shaw Research Preparing free energy perturbation Define Perturbation Plan Calculation Step 1 Display the ligand and its receptor if any in the Workspace Pick the attachment bond to define the core and the step 2 substitution group bond 0 pt on Step3 Select fragments that will replace the substitution group Fragment library 9 items litem selected Fragment Name The core and substitution groups are connected by a single bond called the attachment bond green arrow Developed by D E Sha
35. run simbox dat ub JobId 6 drdws024 0 4a12d59b Apti Desmond run cpt Sub JobId 7 drdws024 0 4a12d684 clickme dtr Last updated Tue May 19 13 27 52 2009 frame000000000 Pause Resume Stop Kill E Update m Delete 4pti Desmond run 5 out tgz Apti_ Desmond run 6 out tgz 4pti Desmond run 7 out tgz Apti Desmond run out cfg A4pti Desmond run log A4pti Desmond run ene A4pti Desmond run out cms 4pti Desmond run mon maegz Close Help D E Shaw Research Simulation Steps Monitor the simulation Ed Monitor Jobs Details File drdws024 0 dmi 2d2cc 2009 05 19 11 39 56 Jobs 2 1 gt gt gt gt drdws024 0 4al2d2fb teas completed finished 2009 05 19 11 40 43 drdws024 0 4a12d329 ipti Desmond run 4 Teom finished 2009 05 19 11 41 29 drdws024 0 4a12d3fd 4pti Desmond r 0 2009 05 19 11 45 01 are the drdws024 0 4a12d4aa i finished 2009 05 19 11 47 54 2 48120595 Apt finished 2009 05 19 11 51 55 relaxation phase 4 Show obs from this project only Monitor Pause Resume Stop Kill Update Delete Close Help D E Shaw Research Simulation Steps Monitor the simulation Jobs Details File File u nyc kolossva Desmond 2 2 Tutorial 4pti Desmond run multisim log running at reduced cpu priority Desmond Panel Job launching command List of files SCHRODING
36. structures o e Step3 Select fragments that will replace the substitution group my fep Job solvent ms defines a series of Rees simulations involving the ligands in the solvent 8 ne my fep job_complex ms defines corresponding simulations involving the ligand receptor complexes Click Write gt gt gt gt Reset Close Help D E Shaw Research Free Energy Perturbation Running free energy perturbation Three ways of running FEP simulations Write a Desmond configuration file yourself and run the FEP simulation from the command line Use Maestro to generate a Desmond configuration file and run the FEP simulation from the command line e Run the FEP simulation directly from the FEP Setup window by clicking Start D E Shaw Research Free Energy Perturbation Generating a Desmond FEP configuration file v maestro 9 0 108 Academic Use Only proj desres hecmond nrnRav Desmond Tutorial 2 2 Tutorial 2 2 workDesmond job files a SEL Maestro Project Edit View Display Tools Applications forkflows Scripts Help mie OCC L VP RS NL Clean up gg 3 k Desmond i EPIR Minimization Glide Simulated Annealing Impact Molecular Dynamics Jaguar j Raenlica Exchanae Liaison LigPrep MacroModel Protein Residue Mutation by FEP MGPRO i Ring Atom Mutation by FEP Phase
37. x1 Display hydrogens Mone Polar only All gm Ha r Preprocess and analyze structure i X wW Assign bond orders v Add hydrogens Treat metals 73H Selenomethionines Treat disulfides Find overlaps a wW Delete waters 5 A Fill loops Cap termini Ex d Preprocess Analyze Only E vA r Chains waters and het groups M Fiton select Display only selected Pick 7 Metal mode r H bond assignment Exhaustive sampling Optimize xi Sample water orientations Interactive Optimizer r Impref minimization Minimize to RMSD A 0 30 Hydrogens only Force field OPLS2001 A ASN 43 G CA THE GEOMETRY OF THE REACTIVE SITE AND OF THE PEPTIDE GROU middle xy rotate ctri middle z rotate right xy translate right click on atom spot center right click on ato Reset Close Help Simulation Steps gt aestro 9 0 107 home ist ae l LX Jy Prepare for simulation Prepare protein Select Workflows gt Protein Preparation Wizard The Protein Preparati appears D E Shaw Research Prepare protein Protein Preparation Wizar 2X Job prefix prepwizard Operates on Workspace PDB Diffraction data Import Browse Display hydrogens None Polar only All Preprocess and analyze structure Iw Assign bond orders Add hydrogens Treat metals Selenomethion
38. 0 107 test prj home istvan buffer Desmond 2 2 Tutoria LX E PAT SIO ST ae ee Maestro Project Edit View Display Tools Applications Workflows Scripts Help Job prefix prepwizard Operates on Workspace iw AD OQO0CO t g m b O COS AM X R adi H h 0 gt H PDB Diffraction data Browse Display hydrogens None Polar only All Preprocess and analyze structure Assign bond orders v Add hydrogens Treat metals Selenomethionines Treat disulfides i Find overlaps Delete waters 5 A Fil loops v Cap termini Preprocess Analyze Only Selected water Le ae ae DES Ww Fit on select Display only selected Pick Sr Shown with lt hd v Chain Name 2 E S Hydrogen 4 bond i T Metal mode _ Delete Selected H bond assignment Exhaustive sampling Optimize ls E J Sample water orientations Interactive Optimizer r Impref minimization Minimize to RMSD 0 30 Hydrogens only Force field OPLS2001 Selected 1 water Atoms 751 1081 Entries 1 3 Res 120 Chn 1 Mol 61 Chg 6 0 middle xy rotate ctri middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Reset Close Help DE shaw 1 Simulation Steps Prepare for simulation Prepare protein B maestro 9 0 107 test
39. 1 30 11 Delete patch Select Extensions Modeling gt gt gt E e Melende Graphics Display Mau Automatic PSF Builder lt U nnl 7 Crue Select the Add solvation box and Add neutralizing lons options Click the I m feeling lucky button gt gt Ee Building Systems with VMD D E Shaw Research Preparing molecular systems with VMD d VMD 1 8758 O SP aY 5 e x M p t Building Systems with VMD DE Shaw Research Preparing molecular systems with Select File ave Coordinates Select mae from the File Type field Give the file a name Click Save gt 935 FE New Molecule Selected atoms Save Coordinates File ty De Save State You can also issue this command from the VMD text window vmd animate write mae my output file mae Process the Maestro file with Mparr and the build constraints script to add force field parameters and constraints DE Shaw Research Building Systems with VMD Loading files into VMD from scripting interfaces Start Python gopython Load the molecule module and read structure file import molecule molid molecule read molid 1 filetype mae filename structure cms molecule read molid filetype dtr filename trajectory dtr wait for 1 Specify a range of frames to load molecule read molid dtr trajectory dtr beg 5 end 55
40. 12 Analyze results D E Shaw Research Simulation Steps Start Maestro e SXCHRODINGEM maestro e SSCHRODINGER maestro SGL over network Simulation Steps Start Maestro v maestro 9 0 108 proj desres Desmond DropBox Desmond Tutorial_2 2 Tutorial_2 2_work Desmond_job_files e m Maestro Project Edit View Display Tools Applications Workflows Scripts Help UA me m A i t A To H n zH HH H H TT T d M uu H at Maestro main window gt gt gt Aa M SR a Atoms 0 0 Entries 0 0 Res 0 Chn 0 Mol 0 Chg 0 Jobs 0 0 Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold D E Shaw Research Import a structure file v maestro 9 0 108 proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files E m Select Project Import gt gt gt gt Edit View ae Tools Applications Workflows Scripts a 7 Structures V II Lal sr E oO p A 7 SEU T Gr DC X X Sod s DX TPRE DC H at Atoms 0 0 Entries 0 0 Res 0 Chn 0 Mol 0 Chg 0 Jobs 0 0 Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold D E Shaw Research Import a structure file hamer stvan bu nd_2 2_ Tutorial O 6 53 E panel appears 59 scr
41. 799 Entries S 1 4 Res 1116 Chn 2 Mol 120 Chg 23 Jobs 0 0 4 1504 A XMEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEOFBDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILI a ANAIVGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRA VNODKKNMLFSGTNIAAGKALGIVATTGVSTEIGKIRDOMAATEODKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIA VALAMBBEBEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKND KPIRSGOFDGLVELATICALCNDSSLDFNETKGVYEKVGEATETALTTLVEKMNVFNTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCS PAKSSRAAVGNKMFVKGAPEGVIDRCNYVRVGTTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGM a Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research 0 41 ICI Setting up membrane systems Automate membrane placement for positioning two or more membrane vaania proteins exactly the same in the bilayer Predefined OPC 300K e g mutagenesis studies E ES Transmembrane atoms ASL optional Place Automatically Place on Prealigned Structure Iw Adjust membrane position Click the Save Membrane Position gt gt gt gt Save Membrane Position to Selected Entries 0 Selected Entries button In the Load Membrane Position from Selected Entry Set Up Membrane window ok Cancel Heb For subsequent proteins click t
42. Absolute size Distances Mioa b 10 0 Angles 90 0 beta 190 0 Box volume 158881 A Calculate ci 10 0 Minimize Volume w Show boundary box except truncated octahedron Use custom charges Preparing a Desmond Simulation System Builder opens gt gt D gt System Builder generates a solvated system that includes the solute solvent and counter and salt ions D E Shaw Research Selecting solutes and solvents The current contents of the Workspace constitute the solute visible or not visible Supported solvent models include SPC TIP3P and TIP4PEW water and organic solvents DMSO methanol and octanol Viparr allows TIPSP and other water models Custom models are allowed if you provide a pre equilibrated simulation box of a different solvent molecule D E Shaw Research Preparing a Desmond Simulation Defining the simulation box Goal Reduce the volume of solvent while ensuring that enough solvent surrounds the solute so that the protein does not see a periodic image of itself during simulation e Minimize solvent volume by Selecting shape that is similar to the protein structure Applying a reasonable buffer 10 A the typical Coulombic interaction cutoff for long range electrostatic calculations Clicking the Minimize Volume button in System Builder Applying the truncated octahedron box shape DE Shaw Research Preparing a Desmond Simulation System
43. Builder output format Composite model system file with extension cms Total solvated system decomposed into 5 sections Protein solute Counter ions Positive salt ions Negative salt ions Water molecules e QPLS AA force field parameters are also written to CMS file D E Shaw Research Preparing a Desmond Simulation Adding custom charges gt Specify custom charges in the custom charges section of System Builder System Builder Set Up Membrane elete N dentify the charge to use m Specify subset of atoms for 5 predefined SFE 5 Custom 000000000 Browse Boundary conditions which custom charges will be applied using Select panel Ma M Box size calculation method Buffer Absolute size a 10 0 c pe b HE Distances Angles Preparing a Desmond Simulation D E Shaw Research Adding tons Add ions using the lons tab of System Builder C System Builder Solute is neutralized by default Excluded region Add an arbitrary number Exclude ion and salt placement within 7 0 Ajof of counterions if there isa WEE reason not to neutralize Add background salt by setting the salt concentration in the Add Salt section Specify the type of positive sak concentraron pas w Salt positive ion Na satt negative ion cl or negative ions to use lon placement C None Neu
44. Chg 23 Jobs 0 0 1 1S a ARESA St E DOVKRE EKYGHNELPAEEGKSLWELVIEOFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILIANAI 1 1502 Wh MGy aD mg G 9 ARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRAVNODKKNMLFSG 1 1501 TN KAK A7 JOMAATE DKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIPEGLPAV H ISQENM See ICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKNDKPIRSGOFDGLVELATIC 4 1504 A AGCNDSSLOFNELKGV GEATzi aAnurir nvnKMNVENTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCSPAKSSRAAVGNKMFVKGAPEG 4 4 A VIDRCNYVRVGTTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGMLDPPRKEVMGSIQLCRDAGIRVIM Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Missing Residues amp Side Chains D E Shaw Research Running Prime Apply Prime to the truncated Isu4 protein structure with the missing loop Simple Proteins with missing side chains no missing residues Complex Proteins with missing residues D E Shaw Research Missing Residues amp Side Chains Proteins with missing side chains Running Prime hd 9 0 108 CEU ICA zs proj desre v Di Toc Applications A PO O_O Aa o cao orkflows Scripts Help Select Applications Prime Refinement e Refinement Select Predict side chains from Task Predicts chains
45. D E Shaw Research Setting up membrane systems ere ee m 5 ETC NES EX ME y ae protein Preparation Wizard PEERS Wizard LLL SERERE E ex Maestro Project Edit View Display Tools p Job prefix prepwizard Operates on Workspace P dio lal lal RC et ES D at x LM ds PDB 1su4 Diffraction data Import Browse nd rt 5k 8 E Y Display hydrogens None Polaronly All Preprocess and analyze structure Iv Assign bond orders v Add hydrogens w Treat metals Selenomethionines Treat disulfides w Find overlaps Delete waters 5 A Fill loops v Cap termini Preprocess Analyze Only i r Chains waters and het aroups Ww Fiton select Display only selected Pick 3 NA 997 Metal mode Delete Selected Delete the selected gra H bond assignment a Exhaustive samplin cet Optimize 37 m TI Ww Sample water orientations Interactive Optimizer mpref minimization to RMSD A 0 30 Atoms 7791 7791 Entries 1 1 Res 1114 Chn 1 Hydrogensoaly Force teld OPLS2001 See plu 1 Displaying state IJ d Close Membrane Systems Sodium ion is just an artifact of the crystal
46. DTPPKREEMVLDDSSRFMEYETDLTFVGVVGML zr w Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold2menu D E Shaw Research Importing membrane placement from OPM maestro 9 0 108 proj desres Desmond Dro pBox Desmo nd_Tuto rial 2 2 Tutorial 2 2 work Desmond jo b files T P BE x Maestro Project Edit View Display Tools Applications Workflows Scripts Help rey H 0 H von A ae 0 1 i 2 WEE IR 0 4 A u i Rt e Wu 5 T H bn A L E 0 2 f n Ls P LN c ES ib e Select To Delete Hom Bia x isis LESS Pom bia Entry Substructure Set Molecule number Molecule type Add olo xyz Molecule number in entry mm Ets a de Molecular weight DUM i586 Subtract Size number of atoms Molecule type Water 117 Intersect Lpda te Markers Atoms matching 1586 TSS oi YP FO BME ASL X Show markers res pt DUM Ato Proximity 6 1 0 Create Set All Unda Redo o middle xy rotat m Matching 1586 atoms Membrane Systems Remove dummy atoms Click the X icon 222 lick the Molecule tab Select Molecule type gt gt and select DUM and click t
47. EETITAFVEPFVILLILI 5 1su4 J XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 5 Isud A ANAIVGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRA 5 1su4 J XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 5 IsuJd A VNODKKNMLFSGTNIAAGKALGIVATTGVSTEIGKIRDOMAATEODKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIA 5 1su4 J XXXXXXXXXXXXXXXXXXXXXXXXXXXXX Commands oa rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Membrane Systems Setting up membrane systems Maestro Project Edit View Display Tools Applications Workflows Scripts Help PA t o H 9 0 H REED ORE ee f fi T A 0 CASOS R MG u o XH bi es A PRETE W 1 H H H H System Builder puts the center of gravity of the solute at the center of the simulation box Non spherical systems appear to shift toward one side of the simulation box Thi i if IS IS a VISUa arti act Atoms 142359 148467 Entries 1 5 Res 35331 Chn 3 Mol 34359 Chg 0 Jobs 0 0 e e e 5 lsu4 A XMEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEOFBDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILI ri 0 C 0 1 d CO n 0 ns 5 1su4 J XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
48. ER utilities multisim JOBNAME 4pti Desmond run host swdev maxjob 0 cpu 2 2 2 i 4pti Desmond run cms m 4pti Desmond run msj cfg 4pti Desmond run cfg description Desmond Panel o 4pti Desmond run out cms NICE cre ated by Booting the multisim workflow engine multisim version 3 2 E mmshare version 18108 t e JO Jobname 4pti Desmond run Username kolossva Master job host drdws024 nyc deshaw com Subjob host swdev Job ID drdws024 0 4a12d2c0 multisim script 4pti Desmond run ms j Structure input file 4pti Desmond run cms CPUs per subjob 222 Monitor Pause Resume Stop Kill Update Delete Close Help D E Shaw Research Simulation Steps The Maestro environment maestro 9 0 108 projidesres Desmond DropBox Desmond_Tutorial_2 23 Tutorial_2 2_work Desmond_job_files ex Horizontal toolbar gt gt gt gt gt Vertical toolbar 22 z3 toms Entries 0 0 Res 0 Chn 0 Mol 0 Chg 0 Jobs 0 0 Command line D E Shaw Research Learning Maestro v maestro 9 0108 pro KEYP Maestro Project Edit View Display Tools Applications Workflows Scripts Help F 1 H 0 0 H A ue car ee gm p A 0 I 2 NEN E 7 t EN 2 H TH 1 J a i t t Y RR ictu o u H mH H A O T A THR 212 C CA CRYSTAL STRUCTURE OF CALCIUM ATPASE WITH TWO BOUND CALCIUM IONS Commands middle xy
49. Istvan Kolossvary D E Shaw Research 71 Desmond 2 2 Tutorial Workshop Desmond DEShawResearch com Introducing Desmond Molecular dynamics simulation system Integrated with Maestro modeling environment compatible with VMD visualization amp analysis tools Long scale simulations of small molecules proteins nucleic acids and membrane systems Study interactions of complex molecular assemblies Advanced simulation techniques FEP simulated annealing replica exchange steered dynamics D E Shaw Research Simulation Steps Import a molecular structure file Prepare refine the structure for simulation Immerse the protein in the membrane Generate a solvated system with PBC Neutralize the system and add salt Assign force field parameters Configure simulation parameters Launch Desmond job Simulation Steps D E Shaw Research Structure Preparation Input Structure File F3 Prepare the structure WETS file for simulation Structure File EJ Refine the prepared structure file PJ Handle ligands or Pecos 9 Assign force field parameters 10 Configure DESMOND to the structure using Maestro simulation parameters E Fill in missing residues or Viparr and side chains 6 Setup the membrane 3 Solvate the system 8 Distribute counter ions m Maestro tasks a DESMOND specific tasks 11 Relax minimize your system and run the Desmond simulation
50. KGVYEKVGEATETALTTLVEKMNVF NTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCSPAKSSRAAVGNKMFVKGAPEG 4 1504 A VIDRCNYVRVGTTRVPMTGPVKEKRILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFME YETDLTFVGVVGMLDPPRKEVMGSIOLCRDAGIRVIM E Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Missing Residues amp Side Chains Running i Select Applications Prime F F2 Refinement A Select Refine loops from the Task field m 9 e A A 5 0 5 Select the loop you want to r ef wwe lick Load from Workspace Estimated processing time for Default sampling 7 hrs 21 min 1 GHz P4 Start Write Atoms 123 30939 Entries S 1 4 Res 1114 Chn 2 Mol 235 Chg 73 4 19U4 A MEAAHSKSTEECDAYFGVSETTGDTPDOVA ONAL zi SLPSVETLGCTSVICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKNDKPIRSGOFDGLVELATIC iG ALCNDSSLDFNETKGVYEKVGEATE TALTTLVEKMNVFNTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCSPAKSSRAAVGNKMFVKGAPEG VIDRCNYVRVGTTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGMLDPPRKEVMGSIOLCRDAGIRVIM E middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Missing Residues amp Side Chains D E Shaw Research
51. KVGEATETALTTLVEKMNVFNTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCS STTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGM EID z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Membrane Systems te ee Ve Ed Project Edit View Display Tools Applications Workflows H Q 0 H r C COD 0 7 R MICH cb H A U Show Ribbons for Selected Residues show Ribbons for Displayed Residues Display 5 Undisplay Atoms Display Side Chains and Portion of Backbone Only Delete Ribbons secondary Structure Chain Name CA Atom Color Residue Charge Residue Property Residue Type Residue Position Entry Constant Color maestro 9 0 108 proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files Maestro middle xy rotate ctrl mi Turn off ribbon view to see candidate selection in the Workspace D E Shaw Research Setting up membrane Lips ERXEEEARERARREAEREREARRAEAEAEAERAEARARREREAEAEAAARRARREEAERAARARAERAERERAAASAGGGGREAEAEAEARAEAEAEAEAS 9 IS vmm 9 0 108 projides mond DropBo zn 2 2 wo 1 mp files Maestro Project Edit View Display Tools Applications Workflows Scripts Help f A ali gt tZ OQ D 0 i da i ihn A 582 SY Ba CA EZA 5 R V HNO a
52. Options the Task field x Use implicit membrane Set Up Membrane EE Residues for side chain refinement ASL All Selection Previous x Pick Residues X Show markers FL 2 rA FO SX Select Residues with Missing Atoms Atoms 120 7752 Entries 1 4 Res 1109 Chn 1 Mol 117 Chg 2 4 1504 A Click Start Comman ds middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Missing Residues amp Side Chains Proteins with missing residues Running Prime v se tc projecta proj desre l 1 Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files PP BEI D Tod Applications orkflows Scripts Help e e Maestro e Select Applications gt Prime LI ee Ge gt ee 5 CO OOOO MR File Edit Display Step Structure Prediction E al RA Input Sequence Input one or more sequences and select the query sequence From Workspace 5 1 5 5 Read a protein sequence file FASTA PDB NEXUS PHYLIP etc lick From File to read in sequence v LITT Sequence From File AA Look in SS proj desres De smond_job_files iba O o fa E 8 fj prepwizard workdir Select the original PDB file gt 4pti pdb prepwizard log Launch Directory Workin
53. Res 3 Chn 1 Mol 1 Chg 3 JjJobs 0 0 Commands Pick a bond to adjust a dihedral Adjusting the conformation of the mutant hdd Maestro 9 0 108 Academic Use Only proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 22 workDesmond job files D E Shaw Research m Adjusting the conformation of the mutant Adjust the torsion angle manually using the Adjustment Tool s Quick Torsion option Hold down the left mouse button and move the mouse horizontally or Rotate the mouse wheel Relax the unfavorable contacts iteratively with rotations about different bonds in the side chain Free Energy Perturbation DE Shaw R esearc h Adjusting the conformation of the mutant ad maestro 9 0 108 Academic Use Only proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files Maestro Project Edit View Display Tools Applications Workflows Scripts Help F 9 0 H PIN fw fe m ASSI E lt z0 I i C R t s v Wy as ox ula H bu A O et xr E M M i N 23 y 5 X U Atoms 49 49 Entries 1 3 Res 3 Chn 1 Moll Chg 3 Jobs 0 0 Commands j Pick a bond to adjust a dihedral n 9 m i k 1 D E Shaw Research
54. Research Free Energy Perturbation Running FEP simulation from the command line e Run FEP simulations using a msj command script file SSCHRODINGER utilities multisim JOBNAME jobname max JJO E OD cpu cpu HOST L S 0 0 host hostname 1 jobname mae m jobname ms o jobname out mae jobname I the name of the job maxjob IS the maximum number of subjobs that can be submitted simultaneously 0 means no limit cpu I the number of CPUs per subjob 8 CPUs can be shown as 2 2 2 HOST localhost means the master Job runs on your local workstation host hostname IS the host or queue where the simulation Jobs will run o apply non default FEP parameters or change the number of Lambda windows add the cfg lt config_file gt option and provide the name of the file generated by the FEP window D E Shaw Research Free Energy Perturbation Computing free energy difference Run the bennett py script from the command line to process the energy file output of the different Lambda runs and compute the free energy SSCHROD INS run FROM desmond bennett py 6 or from Maestro import the out cms file and the delta free energy difference can be displayed in the Project Table he delta delta G relative binding free energy difference is equal to delta G complex delta G solvent D E Shaw Research Free Energy Perturbation reating a custom fragment group
55. VERHLEEYGHNELPAEEG MU we r M M Search for or import sequence homologs then select an appropriate Dm Find Homologs p 3 2 PETAR E modeling path Search Click Import Query family name Homologs amp A Fr prepwizard_workdir d ERLE Select the truncated structure file 1su4_ missing_loop pdb Launch Directory Working Directory Atoms 120 7752 Entries 1 4 Re MEAAHSKS VGVWOERN TNIAAGKA k GH C DP zi 4 1504 A ile name 1su4 missing loop pdb Open lick Open Files oftype PDB pdb ent Cancel middle xy rotate ctrl middle z rotate right x D E Shaw Research Missing Residues amp Side Chains Proteins with missing residues Running Prime vv maestro 9 0 108 Tutorial project prj proj desres Desmond DropBox Desmond_Tutorial_2 2 Tutorial_2 2_work Desmond_job_files S 0 x Maestro Project Edit View Display Tools Applications Workflows Scripts Help e Pd ft Rt fa ey Pa ed 5 a my A Ea CQ Q CJ C3 C3 4 othe Ick the column for the ta MO il Pred CE EEE e ERES ellow line to see the ee ER Aj AnaL L Lll L E y p D EH 2M ds I 2 h Vz FERESTE sequence alignment at the ERE S
56. XXXXXXXXXXXXXXXXX 5 1sul A ANAIVGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRA 5 1su4 J XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 5 1su A VNODKKNMLFSGTNIAAGKALGIVATTGVSTEIGKIRDOMAATEODKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIA T 5 1su4 J XXXXXXXXXXXXXXXXXXXXXXXXXXXXX E Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Membrane Systems Importing membrane placement from OPM The OPM database at the University of Michigan has high quality membrane placements nes OPM database Mozilla Firefox 3 http opm phar umich edu A Support Navigate to vut tS http opm phar umich edu gt 2 DOWNLOAD OPM FILES CONTACT US LIPID COMPOSITION ATLAS Orientations of Proteins in Membranes OPM database HOME ABOUT OPM Protein Classification Types 3 types OPM provides spatial arrangements of membrane proteins with Classes 10 classes respect to the hydrocarbon core of the lipid bilayer Supertamilies 197 auos OPM includes all unique experimental structures of superfamilies transmembrane proteins and some peripheral proteins and Families 281 families i membrane active peptides Features Species 271 species Localization 22 types All proteins
57. XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 5 Isud A ANAIVGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRA 5 1su4 J XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 5 IsuJ A VNODKKNMLFSGTNIAAGKALGIVATTGVSTEIGKIRDOMAATEODKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIA are re ad i ly sati fi ed 5 1 sud J XXXXXXXXXXXXXXXXXXXXXXXXXXXXX Commands Pins middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Membrane Systems Setting up membrane systems bd maestro 9 0 108 proj desres Desmond DropBox Desmond_Tutorial_2 2 Tutorial_2 2_work Desmond_job_files 0O Maestro Project Edit View Display Tools Applications Workflows Scripts Help 1 7 H 9 o H NUR E t te gt l a R OS wow n o XH A H n a 1l 4 VJ g J H H H H Membrane systems should be equilibrated for an extended period of time to resolve the transmembrane hole G up to a few hundred ns a 4 Atoms 30700 148467 Entries 1 6 Res 35331 Chn 3 Mol 34359 Chg 0 Jobs 0 0 5 lsud A XMEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEQFBDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILI 4 5 1su4 J XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
58. Z nd hold menu A Import a structure maestro 9 0 tr INOIT 8 Maestro Project Edit View Display Tools Applications Workflows Scripts Help 4 1 H 0 0 H Pr eS ES a 0 1 z p 1 gt u H CUN d H oN GEH E Iv K y 1 H H H H A LI OQ Lf 3C Atoms 60 514 Entries 1 1 Res 118 Chn 1 Mol 61 Chg 6 Jobs 0 0 middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond a D E Shaw Research Download a structure file J maestro 9 0 108 proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files im e Select Pro ect gt Get PDB gt gt gt gt astro Project Edit View Display Tools Applications Workflows Scripts Help F i FI tat i A i GE us QU DU UM H H H as a 2 2 B xcrne 6 H heed H H En fy E ES ad J Eg current directory and then automatically import it Enter identifier gt 559 en Retrieve from local installation Select the Download gt gt 99 o owra ton we from Web option Cancel Click Download Q oq a Atoms 0 0 Entries 0 0 Res 0 Chn 0 Mol 0 Chg 0 Jobs 0 0 Commands jmiddlezxy rotate ctrltmiddle z rotate right xy translate right click on atom spot center right click on atom bond and hold D E Shaw Research Simulation Steps Prepare for simulation Delet
59. ayer A 3 AL x Os E RYSTAL STRUCTURE OF CALCIUM ATP B RYSTAL STRUCTURE OF CALCIUM ATP T RYSTAL STRUCTURE OF CALCIUM ATP Select the In column to display the entry in the workspace HL Rei a p M OM r The Project Table opens Each row an entry Entries are created sequentially Computational tasks can be applied to the state of an entry selected in the table 90 7 Entries 3 total 3 shown 1 selected 1 included Groups total 0 selected D E Shaw Research Learning Maestro ure height Useful tools in Maestro e Maestro Save Image saves a screen capture of the workspace Project Make Snapshot saves the current project state Edit Clean Up Geometry generates 3D models of hand drawn structures Edit Command Script Editor enables powerful scripting Display Surface generates a variety of molecular surfaces Tools gt Sets defines arbitrary sets of atoms for quick rendering Tools gt Protein Structure Alignment superposes homologue protein structures e Tools gt Protein Reports generates useful structural information in a table Applications Glide is a versatile fast docking tool Applications gt LigPrep prepares small molecules for simulation Applications gt MacroModel offers molecular mechanics tools o Scripts menu for accessing Maestro functionalities from Python scripts D E Shaw
60. choice zm To select abita SYP atoms choose Select Chains J Molecules EAT ETILE E o 5B uw x o LIS 2222 then make complex selections on the tabs including SMARTS and convert selections to ASL Create Set All Undo Redo Clear Invert Previous Selection Atom Num Res Num Matching 7729 atoms Bk Cancel Help D E Shaw Research Learning Maestro Editing a molecular structure hd maestro 9 0 108 proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond joh file Maestro Project Edit View Display Tools Applications Workflows Scripts Help Tools for building gt 2229 GC GC XE A El e d amp editing structures appear when you dick the Hammer Hand draw structures Set chemical elements Increment decrement bond order or formal charge Adjust the position of atoms lean up 3D geometry Add common molecular fragments D E Shaw Research Learning Maestro Maest ject e Projects record every change 0 molecu lar maestro 9 0 108 propdesres Desmond DropBox Desmond_Tutorial_2 2 Tutorial_2 2_work Desmond_job_files Maestro Project Edit View Display Tools Applications Workflows Scripts Help structures and results of 2 ERR EOLA 0 000 3 computational tasks 21 t lick the Project lt Tm Table Select Entry Property Group ePl
61. d maestro 9 0 106 Tutorial project prj projjdesres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 workDesmond job files LL 0 Maestro Project Edit View Display Tools Applications Workflows Scripts Help an eC oe A E A O O gt C C ES fe gt ft Ort RA r m ow Qs X Valu B 4 TTT EEE RA aw Table Select Entry Property Group ePlayer Q Q P A os E ERI je n TI iid M a Ge NI hk 2 EE HM4 4 ODL DDL le Je de gt gt i 0 x m IN adt es MAY CRYSTAL STRUCTURE OF CALCIUM ATP a 5 2 CRYSTAL STRUCTURE OF CALCIUM ATP CRYSTAL STRUCTURE OF CALCIUM ATP Make sure the last entry in the Project Table is included in the Workspace E isuiA Build Struct fL T fab 2D structure height Close Help Entries 5 total 5 shown 1 selected included Groups O total 0 selected Atoms 123 30939 Entries S 1 4 1504 A MEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEQFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILIANAI 4 1504 A VGVWOERNAENAIEALKEYEPEMGKVYRVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRAVNODKKNMLFSG 4 1504 A TNIAAGKALGIVATTGVSTEIGKIRDOMAATEODKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIPEGLPAV 4 1504 A ITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTINOMSVCKMF I IDKVDGDFCSLNEFSITGSTYAPEGEVLKNDKPIRSGOFDGLVELATIC 4 1504 A ALCNDSSLDFNET
62. e systems for each mutant and computes 6 carboxy P binding free energy difference between reference ligand and each selected mutant 9 hydro Ije S with respect to the receptor Desmond DF Shaw Research Click Start gt gt gt gt qm E Reset Close Help D E Shaw Research Free Energy Perturbation Preparing free energy perturbation Desmond uses Bennett s acceptance ratio method for FEP calculations hed Ligand Functional Group Mutation by FEP Start ess PISOS ESI 2 Numerous independent Lambda ipe window simulations will be run Master job for d SI n gle F E calcu lation 2 master jobs to submit for In complex and In pure solvent calculations Name de smond fep jab Username kolossva Host localhost 1 Use the subjob host Tp swdev 64 CPUsj subjob 8 Details gt gt Control how many gt gt gt gt Maximum simultaneous subjobs 0 simulations can run mr cancel simultaneously DE SESS IDEE SO 0 no limit Click Start D E Shaw Research Free Energy Perturbation Preparing free energy perturbation If you click Write these files are written Er my fep job_lig mae contains the original ligand ne igand and its receptor tam inte Workspace and one or multiple mutants Pack X cries ROM 0 oars APTA Step 2 substitution group my fep Job cmp mae contains the receptor and iv Pick the attachment bond ligand
63. e User Manual SCHRODINGER docs prime user_manual pri2 __user_manual pdf DE Documentation Resources
64. e ribbons Switch to ball and stick view for clarity Color carbons green in the structure Prepare the protein for simulation Assign bond orders Add hydrogen atoms Remove crystal waters Ete DE Simulation Steps Prepare for simulation Delete ribbons Maestro Project Edit View Display Tools Applications Workflows Scripts Help 4 1 H 9 0 H a Pr OO Oey OO A piis gt gt P ide To HH M o XH n A L CJ amp 7 J UR 3d E bat odis H UH H H HH 9 Show Ribbons for Selected Re 85 show Ribbons for Displayed Residues Display Atoms Undisplay Atoms Display side Ghains and Portion of Backbone Onlv Delete Ribbons secondary Structure Chain Name CA Atom Color Residue Charge Residue Property Residue Type Residue Position me Entry ze lick on atom bond and hold menu B N E Constant Color p JH TIU ADEE AS J a t i AN al 1 L IQUIVIT D E Shaw Research Prepare for simulation Change view aestro 9 0 1037 nom Js EET Ji pe n T T Maestro Project Edit View Display Tools Applications Workflows Scripts Help 1 1 E H 0 0 H VS c s SUP SAS gt gt COS H TH OSH A H bn A 2 7 VJ 1 8 ll 3l EN Y I H H H H T
65. een shots 18U4 pdb 1su4 opm pdb 5 4pti pdb Select PPB gt gt 553 LL Simulation Steps Import a structure file Look in hamer stvan bu nd_2 2_ Tutorial 000 f screen shots e 18U4 pdb Select the structure gt d ed flle you want to Import af Options File name 4pti pdb D E Shaw Research Simulation Steps Import a structure file homelstvan bu nd_2 2 Tutorial Q A 8 mm screen shots o 03 _ 18U4 pdb 1su4 opm pdb 4ptipdb DE Simulation Steps Import a structure file The Import Options panel appears gt gt gt gt 00 11 EETES Import all structures 3 Replace Workspace 3 Fit to screen following import Start i Import only first Desmond structure End Total EN Include in Workspace First Imported Structure Create groups for Files with multiple structures m Import associated data files Read alternate locations For SD import create titles from SD molecule name SD property Click Close when done 525 D E Shaw Research Simulation Steps Import a structure file homelstvan bu nd_2 2 Tutorial Q A 8 mm screen shots o 03 _ 18U4 pdb 1su4 opm pdb 4ptipdb Click Open gt 9 35r nee m cre DE Simulation Steps file d
66. g Directory Next Build Structure Any z Cancel Click Open Nm middle xy rotate Files of type DE Shaw Research Missing Residues amp Side Chains 0 Structure Prediction runi m 8 File Edit Display Step MEM cH us Iw d m 1 1 1 1 i 1 L 1 1 L 1 L oe 6 6 GEREN SEHEDE 15U4 A a x x oe Q Q v P Input Sequence Input one or more sequences and select the query sequence E dit Build Alignment Structure Fold R E cag nition Comparative Modeling Threading Proteins with missing residues Running Prime v 7 Tutorial project prj proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files Maestro Project Edit View Display Tools Applications Workflows Scripts Help mr n H 0 4H AX VM UON Sr e Ses A 0 d i 7 A e R e Gp WU u m H bn A O 4 P WP a 4 E Ir cope m i From File From Workspace Sete bep pene Re Here li l ex 9 o 4 olo xyz v N 4 3 4A Qo amp 4 o 4 He Sequences Bat Atoms 120 7752 Entries 1 4 Res 1109 Chn 1 Mol 117 C Input Find Sequence
67. ginal side chain for FEP simulations Manual adjustments to the conformation of small molecules can be readily done in Maestro Use Maestro s Adjustment tool to make manual adjustments D E Shaw Research Free Energy Perturbation Adjusting the conformation of the mutant r 1 1 gt 9 1 nr maestro 9 0 108 Academic Use Only projjdesres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files 777 00 0 0 0 l 6 x Maestro Project Edit View Display Tools Applications Workflows Scripts Help 2 t H 9 0 H MX Py my T A Gh fo X Q PV 5 or 4 3 Eo k E A Gp WH Qui T m H bn A CJ CU VJ SA l e 2 Eik hr p KA 091019101165 angles dihedrals chiralities torsions or rotamers f 90 90 S xyz X A Atoms 49 49 Entries 1 3 Res 3 Chn 1 Mol 1 Chg 3 Jobs 0 0 Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Maestro Project Edit View Display Tools Applications Workflows Scripts Help 4 1 H 9 0 H AN N N OY a 0 1 a Cy Az d gt FH P u bn AE C373 S ld NP Atoms 49 49 Entries 1 3
68. he Add button Click OK DE Shaw Research Importing membrane placement from N b Protein Preparation Wizard EE mx Preprocess with the Protein Preparation Wizard z PDB 15su4 Diffraction data Import Browse Use the structure in the Workspace aene Nowe gt A Preprocess and analyze structure Iv Assign bond orders v Add hydrogens w Treat metals Check options for preprocessing as shown M Selenomethionines v Treatdisulfides v Find overlaps Delete waters 5 A Fill loops v Cap termini 222 do not delete crystal waters Click Preprocess Select the sodium ion in the Het table Click the Delete Selected button 222 Generate Het States Metal mode Delete Selected Jelete the selected gra H bond gnment imize Exhaustive sampling zi Iv Sample water orientations Click Close D E Shaw Research Membrane Systems Importing membrane placement from OPM Select Applications Desmond gt System Builder lick the lons tab Click the Select button Click the Advanced ion placement 222 e button 27 Click the Candidates button 23 hone under Candidates Click OK gt gt gt gt Membrane Systems Importing membrane placement from OPM Select POPC as the membrane model lick the Place on Prealigned Structure button Click OK Membrane Systems Importing membrane placement from OPM Edit View Display To
69. he Load Membrane Position from Selected Entry button D E Shaw Research Membrane Systems Setting up membrane systems Start the membrane system setup E uM ions 6 8 minutes to process this example _ 5 E Set Up Membrane 2 Membrane model i Predefined OPC 300K E Custom Browse Transmembrane atoms ASL optional Place Automatically Place on Prealigned Structure Adjust membrane position amma 30 0 Save Membrane Position to Selected Entries Membrane window Click Start in the itn gt gt gt Lose we ree Builder window Close Help D E Shaw Research Membrane Systems Setting up membrane systems FIFI PIPPI PIER ESP IPP PIP SPIE IPP PI PPP PFEIFER PI PIP IFIP j 5 maestro 90 108 projidesres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 workiDesmond job files REK Maestro Project Edit View Display Tools Applications Workflows Scripts Help esulting sim rotein shown as CPK model m 2 EA SL eS z Bd gir OP an Sos E ue 0 Atoms 142359 148467 Entries 1 5 Res 35331 Chn 3 Mol 34359 Chg 0 Jobs 0 0 5 lsu4 A XMEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEOFBDLLVRILLLAACISFVLAWFEEG
70. in OPM 792 entries Each protein is positioned in a hydrophobic slab of adjustable thickness by minimizing its transfer energy from water to the membrane core Methods D E Shaw Research Membrane Systems Importing membrane placement from OPM iv 1su4 Calcium ATPase E1 2Ca state Orientations of Proteins in Membranes OPM database Mozilla Firefox BEI File Edit View History Bookmarks Tools Help aP AOA E Most Visited 6 CentOS P Support le http opm phar umich edu protein php search 1su4 2 IGI opm membrane UNIVERSITY OF MICHIGAN COLLEGE OF PHARMACY MOSBERG LAB B Search OPM PDB ID or protein name OPM DOWNLOAD OPM FILES CONTACT US LIPID COMPOSITION ATLAS 1su4 Calcium ATPase E1 2Ca state W Type 1 Transmembrane 2 classes Class 1 1 Alpha helical transmembrane 52 superfamilies Superfamily 1 1 08 P type ATPase P ATPase 1 family 3 A 3 TCDB amp W Family 1 1 08 01 P ATPase 9 proteins 3 A 3 TCDB amp W Species Oryctolagus cuniculus 14 proteins m Localization Endoplasmic reticulum membrane 38 proteins 1su4 Calcium ATPase E1 2Ca state Hydrophobic Thickness 290 2 8 A Tilt Angle 23 4 iar 81 0 Kkcal mol Links to 1su4 PDB Sum amp SCOP amp MSD 3D view in Chime Jmol or Webmol jio Sese wsalegy in Endoplasmic reticulum membrane lumenal side cytoplasmic side Membrane System
71. ines Treat disulfides v Find overlaps w Delete waters 5 A Fillloops Cap termini _ analyze ony Chains waters and het groups W Fit on select Display only selected Pick ete zt T S Residue Number DS SU en ut AL get 2d WT Metal mode H bond assignment Exhaustive sampling Optimize IUE W Sample water orientations Interactive Optimizer Impref minimization Minimize to RMSD 0 30 Hydrogensonly Force field OPLS2001 Reset Close Help Simulation Steps Prepare for simulation Check these options Assign bond orders Add hydrogens Cap termini to cap N or C termini Treat metals Treat disulfides Find overlaps Delete waters Click Preprocess D E Shaw Research Prepare for simulation Prepare protein Protein Preparation Wizard Job prefix prepwizard Operates on Workspace PDB Diffraction data Import Browse Display hydrogens None Polar only All Preprocess and analyze structure Iw Assign bond orders Add hydrogens Treat metals Selenomethionines v Treat disulfides Find overlaps Delete waters 5 A Fill loops wW Cap termini Preprocess Analyze Only Chains waters and het groups W Fit on select Display only selected Pick Residue chains and water molecules are listed here HET groups if any are listed here Generate Het States Metal mode Delete Selected H bond a
72. inuously updated in a temporary directory tmpdir username Jobname where tmpdir is specified in SCHRODINGER schrodinger hosts Use LOCAL option to keep job files in the working directory Running Simulations D E Shaw Research Running Desmond simulations e Run multiple jobs from the command line May be necessary for system relaxation and FEP simulations Multiple jobs are handled by the MultiSim facility Reads a ms command script file and runs simulations defined within it SSCHRODINGER utilities multisim JOBNAME jobname max Job f MES O gt cpu cpu HOST localhost host hostname i jobname cms m jobname ms j o jobnamEE out cms maxjob IS the maximum of simultaneous subjobs 0 no limit cpu IS the of CPUs per subjob 8 CPUs can be 2 2 2 hostname IS the host or queue where simulation Jobs will run Running Simulations D E Shaw Research Preparing free energy perturbation Desmond can run free energy perturbation FEP calculations Ligand and amino acid residue mutation Annihilation absolute free energy calculation Single atom mutation in a ring structure e Visually specify fixed and variable parts of a molecule for defining the mutation Store the atom correspondence map in the mae file dual topology D E Shaw Research Free Energy Perturbation Preparing free energy maestro 9 0 108 Academic Use Only proj desres Desmond Dr
73. ion 2 Relaxation protocol Use default protocol Browse system before simulation MES option Desmond Developed by D E Shaw Research Click Start gt gt gt D E Shaw Research Simulation Steps Configure job submission options Outpu Append new entries Name 4pti Desmond run Username kolossva localhost 1 Use the subjob host Subjob Host CPUs subjob 8 Details lt lt The system will be domain decomposed as follows X 2 Y 2 Z 2 Actually needs 8 CPUs subjob Maximum simultaneous subjabs 0 Cancel Simulation Steps Select Append new entries Enter a name for the simulation and select the Master host Select the subjob Host and run options Click Start D E Shaw Research Monitor the simulation to mor 4pti Desmond run idpti Desmond run multisim log E multisim Apti Desmond run multisim che Exit Status finished 4pti Desmond run 2 out tgz Status 0 4pti Desmond run 3 out tgz Status updated 2009 05 19 11 39 44 4pti Desmond run 4 out tgz Job Host drdws024 nyc deshaw com Job Directory scratch kolossva 4dpti Desmond run Job Started 2009 05 19 11 39 44 Job Ended 2009 05 198 12 15 59 JobId drdws024 0 4a12d2c0 Parent JobId None sub JobId 1 drdws024 0 4a12d2cc Sub JobId 2 drdws024 0 4a12d2tfb Sub JobId 3 drdws024 0 4a124d329 E sub JobId 4 drdws024 0 4a12d3fd cese caius Sub JobId 5 drdws024 0 4a12d4aa Apti Desmond
74. lick on atom bond and hold menu D E Shaw Research o P rRAATINVC Alii b ALII 50 107 test Pr j home jistvan butfer Desmond 2 2 Tu lorkflows Scripts Help xc mje M 3 O 3 GonfGen sle muUe e Minimization simulated Annealing Molecular Dynamics Replica Exchange FEP Ligand Functional Group Mutation by FEP Protein Residue Mutation by FEF Ring Atom Mutation by FEP Total Free Energy by FEP Simulation ually Analysis a Epik Glide Impact Jaguar Liaison LigPrep MacroModel MGPRO Phase Prime Primex QikProp asite SiteMap Strike AG luster Monitor Jobs A obs halt uc s a Applications View Display Tools Edit Maestro Project Atoms 752 1062 Entries 1 3 Res 120 Ghn 1 Mol 61 Chg 7 010 middle xy rotate ctrl middle z rotate 0 i translate s ad click on atom OPO oomen ici click on atom bond and hold menu Preparing a Desmond simulation nula D E Shaw Research Preparing a Desmond simulation System Builder solvation lons Set Up Membrane Solvent model None Predefined SPC E Custom Browse Boundary conditions Box shape Orthorhombic Box size calculation method Buffer
75. lization process and should be deleted Select the sodium ion in 1 Click the Delete Selected Click Close D E Shaw Research Setting up membrane systems maestro 9 0 108 Maestro Project Edit View Display Tools Applications Workflows Scripts Help i 4 H 0 b 0 ER wr COE N XH CX HH OUR OH 0 H PN PN M ur s ex A H En A L E f 8 J lL JA E VS I IN Pe Er show Ribbons for Displayed Residues Display Atoms Undisplay Atoms Display Side Chains and Portion of Backbone Only Delete Ribbons secondary Structure Chain Name GA Atom Color Residue Charge 0 0 Residue Property HLEKYGHNELPAEEGKSLWELVIEQFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILI ADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRA Residue Type IGKIRDOMAATEQDKTPLOOKLDEFGEQLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIA IVRSLPSVETLGCTSVICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKND Residue Position GVYEKVGEATETALTTLVEKMNVFNTEVRNLSKVERANACNSVIRQLMKKEFTLEFSRDRKSMSVYCS _ TTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGM Entry Constant Color ler right click on atom bond and hold menu T Iv K mide D E Shaw Research Setting up membrane systems 2 cluded region Exclude ion and salt placement within lick the lon
76. ll Chg 3 0 Commands Pick bond half to define a new grow bond D E Shaw Research Creating a custom fragment o EE gL 2 RSE Atom Residue Properties Properties Fragments Select propyl under Fragments gt gt gt gt gt kee isopentyl ta cyclohexylmethyl 3 cyclohexylpropyl 4 cyclohexylbutyl trifluoromethyl TE hydroxymethyl 2 hydroxyethyl 5 hydroxypentyl 2 ammonioethyl nm protonated 5 morpholinopentyl protonated piperidin 4 yl E Click Close D E Shaw Research Free Energy Perturbation r bd Maestro 9 0 108 Academic Use Only proj desres Desmond DropBox Desmond_Tutorial_2 2 Tutorial_2 2_work Desmond_job_files 0 reating a custom fragment group Maestro Project Edit View Display Tools Applications Workflows Scripts Help p H 9 o H ps Pr Oey OY ERS E T 0 1 A Coy KED A si D gt 2 BA E HH wy o H A H En A our iJ ld 4 7 x as Y 4 90 wy S Atoms 49 49 Entries 1 3 Res 3 Chn 1 Mol 1 Chg 3 Jobs 0 0 Commands Pick bond half to define a new grow bond D E Shaw Research Adjusting the conformation of the mutant Initial conformation of the mutant must be as close as possible to the ori
77. mber Simulation Systems Desmond simulation parameters Set simulation parameters by Using Desmond applications in Maestro Applications Desmond Editing the Desmond configuration file Applications include Minimization Molecular dynamics Simulated annealing Free energy perturbation FEP Replica exchange D E Shaw 6 h Desmond Simulation Desmond simulation parameters TO 9 0 107 home istvan buffer Desmond 2 2 Tutorial Gas Maestro Project Edit View Display Tools Applications Workflows Scripts Help A CC CCV R B e ues i CombiGide 5 OOOO uq 9A GonfGen Desmond System Builder Epik Minimization Select Applications gt Desmond ti Impact gt Molecular Dynamics m Liaison mE S CU SN C RC nd 2527 Wow ee e cu ui hs IOL ut ut ur ur y aut out ut EOR E ut ue aet P utu E EN Dae ee Tus ee Gate eh Tu uu Du Model system 7 Choose Load from Workspace or Load from file click lad gt Load from Workspace Load The system contains 14022 atoms and was set up for nor FEP simulations m Simulation Set simulation options b Simulation time ns total 0 12 elapsed Recording
78. md m mae moll mae mol2 mae f mol3 mae dtr trajectory subdir clickme dtr D E Shaw Research Visualization and Analysis Trajectory analysis with VMD Loading files from the VMD window Select File New Molecule 555 Ww VMD Main Atoms Frames Vol x Click Browse and select the gt 222 structure file Click Load Click Browse again gt gt gt In the Choose a molecule file window select the clickme dtr trajectory flle you want to use Click Load again Determine file type 1 00758 v Preview DropBox sm torial 2 2 OK a Cancel D E Shaw Research Visualization and Analysis D E Shaw Research Help Frames Extensions 102 Display Mouse desmond run outc 14476 Graphics Anti T a C3 E e 3 m os oO 4 c i d o E xL j Iz m Dr LL n gt v VMD 1 57158 OpenGL Display is with VMD lys ectory ana Traj Trajectory analysis with VMD Select Extensions Analysis for trajectory analysis tools elect Extensions Modeling to set u simulation systems in VMD l D E Shaw Research Visualization and Analysis Preparing molecular systems with VMD e Load a molecule into VMD Use VMD modeling tools to generate the simulation system the main building tool is Automatic PSF Builder Save the system in a Maestro file
79. mmetry Current protonation states of ASP gt 2 222 EEE GLU and HIS residues are filled in below as well as OH bond orientations 1s r 2 A SER 47 HG Ann Cyrientatin Pick to locate species Close Help D E Shaw Research Simulation Steps Prepare for simulation Prepare protein nclude ent o On oor ee Mete Use crystal symmetry 30 r ATHRIL rom Initial HE aij r A TYR 21 HH 32 C amp TfR23 HH E E A THR 32 HG1 Initial EIE 14 r A TYR 35 HH Initial 15 r ASER47 HG initial Ann cCruentatin Pick to locate species Close Help Simulation Steps Select an item to focus the Workspace on a residue Flip through protonation states with the arrow buttons D E Shaw Research Prepare for simulation Prepare protein eractiv l AA EDD Prj home an buffer Desmond 2 2 T Orie e H bond Network Optimizer Cz A maestro 9 0 107 a Maestro Project Edit View Display Tools ee Workflows Scripts Help H g PU ne UNE TE e un T 0 xn s A we 4 ld S a Analyze Network Include current orientations fj Only analyze Workspace selection Use crystal symmetry A lad I X View all species 76 species total View cluster idl 4 gt id 30 clusters total z All species 1 Optimize All Degree of sampling Low i High
80. mperature factor disulfide Formal charge disulfidel Partial charge Number of attachments Display state Backbone side chain representation visibility PDB serial segres index het original index water pdb occupancy pdb tfactor disulfide Show markers Wait until the ASL area is filled gt gt gt Click the Selection button CONS S ee ee E ind jp rem num 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 375 376 377 378 379 380 381 382 383 384 385 38D 387 388 389 390 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 jus 410 411 de ae a 415 416 418 n i nn 422 4 fs 425 A27 428 Matching 5019 atoms Membrane Systems D E Shaw Research Setting up membrane systems e e e w lai n 3 5 ks n Maestro Project Edit View Display Tools Applications Workflows Scripts Help f o H 9 0 H D ED SEU AEST EE E Workspace shows the Initial automatic placement for the i protein VS I IN I LI Pr show Ribbons for Displayed Residues Display Atoms Undisplay Atoms Display Side Ghains and Portion of Backbone Only Delete Ribbons secondary Structure Chain Name GA Atom Color Residue Charge Residue Property bs 0 0 Ld nAuSAEILAACISFVLAWFEEGEETITAFVEPFigamm mgM Residue Type RADRKSVORIKARDIVP
81. nce frame all move sel fit ref mass Append new RMSD value rms append sel rmsd ref mass Get positions of CA atoms pos vmdnumpy positions ca pos pos inds Accumulate positions into average if avg is None avg ca_pos Make a copy of ca_pos else avg ca_pos Add this frame s contribution Loop over frames n molecule numframes molecule get top for i in range 1 n molecule set frame molecule get top 1 processFrame Scale the average avg n D E Shaw Research Working with VMD Documentation Resources Desmond Tutorial Desmond Users Guide e Desmond user community website http groups google com group desmond md users e Schrodinger s Desmond documentation Quick Start Guide SSCHRODINGER docs desmond quick_start des22_quick_start pdf Desmond User Manual SCHRODINGER docs desmond user_manual des22__user_manual pdf e Maestro documentation Maestro Overview SCHRODINGER docs maestro overview mae90_overview pdf Maestro Command Reference SSCHRODINGER docs maestro ref_manual mae90_command_reference pdf Maestro Tutorial SCHRODINGER docs maestro tutorial mae90_tutorial pdf Maestro User Manual SSCHRODINGER docs maestro user_manual mae90_user_manual pdf e ASL documentation SCHRODINGER docs maestro help mae90_help misc asl html e Prime documentation Prime Quick Start SSCARODINGER docs prime quick_start pri2 _quick_start pdf Prim
82. ols Applications Workflows Scripts Help H 0 at U 77 1 4 0 0 H D wow d o XH ec H En A L ME amp 2 J I H UH H 29i d X 7 Entries S 1 9 Res 1116 Chn 3 Mol 121 Chg 27 Jobs 0 0 XMEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEOFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILI ANAIVGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRA VNODKKNMLFSGTNIAAGKALGIVATTGVSTEIGKIRDOMAATEODKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIA VALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKND KPIRSGOFDGLVELATICALCNDSSLDFNETKGVYEKVGEATETALTTLVEKMNVFNTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCS PAKSSRAAVGNKMFVKGAPEGVIDRCNYVRVGTTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGM middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Project Atoms 359 15799 8 1504 A m ee i su Commands hd maestro 9 0 108 Iprojdesres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files Maestro D E Shaw Research Importing membrane placement from OPM M AF ANA C 4 PNAC DE Shaw 1 Membrane Systems Membrane Systems D E Shaw Research Importing membrane placement from OPM
83. om spot center right click on atom bond and hold DE Shaw Research Visualization and Analysis Visualization and analysis using Maestro Simulation Quality Analysis v 21101611011 3061111 Ur iii Click the Plot button gt 95 9 73 8928e4 An interactive graphical gt SY 6 C representation of the data E ui 47950 4800 appears E LA 147600 147400 147200 gt 147000 146800 146600 14640 D E Shaw Research Visualization and Analysis Trajectory analysis with VMD e VMD is a widely used molecular visualization platform providing a plethora of tools for trajectory analysis Strong support for atom selections Ability to efficiently animate trajectories with thousands of snapshots Support for Tcl and Python scripting languages Built in capability to write Maestro files useful to prepare simulation system in VMD and read Desmond trajectory files useful for analyzing Desmond trajectories These features are available in the new VMD 1 8 7 D E Shaw Research Visualization and Analysis Trajectory analysis with VMD e VMD Python interface Access from console terminal from which you launched VMD vmd gopython Access from Idle window that runs inside VMD preferred vmd gt gopython command import vmdidle vmidle start Copy command into vmdrc file Some modules are provided by the Python interpreter
84. on D E Shaw Research Simulation Steps Generate a solvated system solvation lons Set Up Membrane Solvent model None Predefined SPC S Custom Browse Select Orthorhombic as gt gt gt Box size calculation method Buffer Absolute size the shape of the solvent Deomm EEE boo foo Angles 90 0 beta 30 0 gamma DOX Box volume 158881 A Calculate Minimize Volume w Show boundary box except truncated octahedron D E Shaw Research Simulation Steps Generate a solvated system 4X System Builder solvation ions Set Up Membrane E Solvent model None Predefined SPC Custom Browse Boundary conditions Box shape Orthorhombic Select Buffer as the method gt gt gt Box size calculation method Buffer amp Absolute size Distances A a 100 5 100 c 100 of calculating the 7 of the Angles alpha 20 0 beta 0 gamma 90_0 Box volume 158881 AB Minimize Volume solve nt box w Show boundary box except truncated octahedron Set the Distances to 10 Use custom charges Select Show boundary box Click Calculate D E Shaw Research Simulation Steps Generate a solvated system maestro 9 0 107 test prj home istvan buffer Desmond 2 2 Tutorial mss Maestro Project Edit View Display Tools Applications Workflows Scripts Help 1 N 7 H 8 0 H 7 v gt Ak EC amp EE Aul ari 6 O O 0
85. opBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files dm Maestro Project Edit View Display Tools Applications Workflows Scripts Help Example ligand mutation r 1 7 H 0 0 H DUE ONE ON A OO VOU CU CORR RGF ah genae This side chain will be muta the NH3 with a methyl gr SH g Atoms 49 4131 Entries 1 1 Res 276 Chn 2 Mol 2 Chg 2 Jobs 0 0 1I entr A I sentr ERGRHOSLOCRSPEEOCLDVVTHWIOI I entr A D fa P Comman ds middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Free Energy Perturbation Preparing free energy perturbation x wv maestro 3 0 108 Academic Use Only proj desres Desmond DropBox Desmond_Tutorial_2 2 T utorial_2 2_work Desmond_job_files 75 Maestro Project Edit View Display Tools Applications Workflows Scripts Help o E H 9 o H NA nmm ary ID A7 gt que PIS HOH N pH Pa nEn A O Ly VJ 202 Jobs 0 0 Atoms 49 49 Entries 1 1 Res 1 Chn 1 Mol 1 Chg 5 Commands Pick atom in molecule to delete D E Shaw Research Preparing free energy Mea v maestro 9 0 108 Academic Use Only
86. periodic m 1 frame 1 dictionary of periodic cell data set periodic m 1 frame 1 Set periodic cell keywords get physical time m 1 frame 1 time value for timestep read molid filetype filename load molecule files write molid filetype filename save molecule files D E Shaw Research Working with VMD Writing structures and trajectories in VMD molecule write molid dtr trajectory dtr waitfor 1 molecule write molid dtr trajectory dtr beg 100 end 1 skip 10 waitfor 1 sel atomsel name CA sel frame 45 sel write mae ca45 mae D E Shaw Research Working with VMD Analyzing whole trajectories in VMD e Script runs through frames in a molecule aligns frames to the first frame and computes the aligned RMSD for each frame and the averaged position of the alpha carbons from atomsel import atomsel import molecule vmdnumpy import numpy avg None holds averaged coordinates all atomsel all atoms in current frame ref atomsel name CA frame 0 dt reference frame 0 sel atomsel name CA alpha carbons current frame inds sel get index indexes of alpha carbons mass sel get mass masses of alpha carbons rms 0 holds RMSD reference frame D E Shaw Research Working with VMD Analyzing whole trajectories in VMD def processFrame global avg Align current frame with refere
87. rce field parameters with Viparr Viparr generates error or warning messages when A residue matches more than one template in a force field A residue name is matched to a force field template with a different name There are unmatched residues A residue is matched by more than one of the selected force fields D E Shaw Research Force Fields with Viparr Generating force field parameters with Viparr option allows you to assign parameters for a particular structure _m_ct block in the input cms file e n option allows you to include comments in the output cms file for annotation purposes You must add constraints in a separate step with Viparr S SSCHRODINGER run FROM desmond build coer alnts py input cms output cms where input cms is the Maestro file with Viparr parameters and output cms includes the constraints D E Shaw Research Force Fields with Viparr Importing AMBER simulation systems e Simulation systems from the Amber Molecular Dynamics package can be imported to Desmond Desmond can convert prmtop and crd files into cms file e Script is called amber prm2cms SSCHRODINGER run FROM mmshare amber prm2cms py p my amber system prm c my amber system crd o outpu ms e Desmond applies force field parameters in one to one agreement with the Amber prmtop file Before simulation add constraints with build_constraints script D E Shaw Research Importing A
88. rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Learning Maestro D E Shaw Research Displaying residue and atom information isplay Tools Applications Workflows Scripts Help T 9 o H Pn tes E e o eH wl H bn A 2 CJ VJ E E 0 d H 3 Atoms 3 7791 Entries 1 1 Res 1114 Chn 1 Mol 116 Chg 22 Jobs 0 0 1 1504 A MEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGK Wisp d mAS MEAN EGEETITAFVEPFVILLILIANAI I ISUJ A VGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDI 7770777750707 vU0mc0770777777 ESVSVIKHTEPVPDPRAVNODKEN I1 18U1 A MLFSGTNIAAGKALGIVATTGVSTEIGKIRDOMAATEODKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIPE I 18U1 A GLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKNDKPIRSGOFDGLVE I ISUJ A LATICALCNDSSLDFNETKGVYEKVGEATETALTTLVEKMNVFNTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCSPAKSSRAAVGNKMFVK E 1 1504 A GAPEGVIDRCNYVRVGTTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSSRFMEYETDLTFVGVVGMLDPPRKEVMGSIOLCRDAG Commands i middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu Learning Maestro D E Shaw Research Changing selection mode ww 0 9 0 108 laa as ea eC Be amp yA Click and hold m El the Select button and make a
89. s membranes HOME ABOUT OPM Protein Classification Types 3 types Classes 10 classes Supertamilies 197 superfamilies Familles 281 families Species 271 species Localization 22 types All proteins in OPM 792 entries Protein Links PDB Sum PDB MSD SCOP Swiss Prot Pfam OCA MMDB In th e resu Its D d ge cl ck Downl 0a d C 0 ordi nates M Save the file to your computer D E Shaw Research Importing membrane placement from OPM M Project Edit View Display Tools Applications Workflows Scripts Help H 9 RR m j 0 H AC s gis c HOH M o XH ec ue SH A L ME 71 8 t H CH H H oU eT o 2 Atoms 1706 9377 Entries 1 7 Res 1907 Chn 4 Mol 1707 Chg 27 Jobs 0 0 6 lsu4 A MEAAHSKSTEECLAYFGVSETTGLTPDOVKRHLEKYGHNELPAEEGKSLWELVIEOFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILIA b Isug A WNAIVGVWOERNAENAIEALKEYEPEMGKVYRADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRAV b Isug A NODKKNMLFSGTNIAAGKALGIVATTGVSTEIGKIRDOMAATEODKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIAV b Isug A ALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKNDK 5 1sudj A PIRSGQFDGLVELATICALCNDSSLDFNETKGVYEKVGEATETALTTLVEKMNVFNTEVRNLSKVERANACNSVIROLMKKEFTLEFSRDRKSMSVYCSP a isu AKSSRAAVGNKMFVKGAPEGVIDRCNYVRVGTTRVPMTGPVKEKILSVIKEWGTGRDTLRCLALATR
90. s tab Click the Select button of LES b lon placement C None Neutralize Add cl Advanced ion placement w Add salt Salt concentration 0 15 M Salt positive ion Na salt negative ion cl Start Write Reset Close Help Membrane Systems D E Shaw Research Setting up membrane systems Atom Selection PILOT TT TTT VEE m ATR Exclude region De SLE ELE E Te Select Molecule gt gt gt Ecc type Select the CA ions The ASL area defines the excluded region Click the Proximity button zI set th to t A Click OK 23 uu Membrane Systems Setting up membrane systems 5 6 System Builder solvation lons Excluded region Exclude ion and salt placement within 7 0 of lon placement Click the Advanced ion placement button Click the Candidates button Shift click to select the LI first 23 residues under gt gt gt Candidates AGLU 183 AASP 818 d Click OK gt gt Tie D E Shaw Research Membrane Systems Setting up membrane Scripts Help pu s 0 0 iHLEKYGHNELPAEEGKSLWELVIEOFBDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILI ADRKSVORIKARDIVPGDIVEVAVGDKVPADIRILSIKSTTLRVDOSILTGESVSVIKHTEPVPDPRA SIGKIRDOMAATEODKTPLOOKLDEFGEOLSKVISLICVAVWLINIGHFNDPVHGGSWIRGAIYYFKIA AIVRSLPSVETLGCTSVICSDKTGTLTTNOMSVCKMFIIDKVDGDFCSLNEFSITGSTYAPEGEVLKND amp GVYE
91. same residue as within 5 of protein molid 0 watl atomsel water and same residue as within 5 of protein molid 1 D E Shaw Research Working with VMD Atom selections in VMD e The atomse1 type takes three arguments Selection Selection predicate Molid Molecule associated with the selection Frame Index of the snapshot referenced by the selection Setting the frame attribute nl len wat0 number of atoms in the selection f watO frame returns 1 watO frame 20 makes watO reference frame 20 n2 len watO0 will be equal to nl watO0 update recompute selection on frame 20 n3 len wat0 might be different from nl e hanging the frame does not cause the selection to be recomputed e Only the update method changes the atoms referenced e Changing the frame does change the result of calculations that depend on the coordinates e g center 0r rmsd D E Shaw Research Working with VMD Atom selections in VMD e Extracting data about a molecule for the selected atoms Get the number of alpha carbons num_ca len ca Get the residue name of each alpha carbon resnames ca get resname Set the type attribute of all atoms to xX all set type X Compute the center of mass of atoms in frame 10 mass prol0 get mass com prolO center mass Align prol10 to atoms in frame 0 compute RMSD proO atomsel protein
92. ssignment EE Exhaustive samplin Optimize f E iw Sample water orientations Interactive Optimizer Impref minimization Minimize to RMSD 0 30 Hydrogens only X Force field OPLS2001 Reset Close Help D E Shaw Research Simulation Steps Prepare for simulation Prepare protein Maestro Project Edit View Display Tools Applications Workflows Scripts Help H 8 0 2 H NON te OS AG 2 EN i 3 5 A gt gt P CO ww o M 1 n aA ul CJ amp 7 J lA S T bw K y H H H Atoms 751 1081 Entries 1 2 Res 120 Chn 1 Mol 61 Chg 6 Jobs 0 0 LA Simulation Steps middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu DE Shaw Research Prepare for simulation Prepare protein Maestro Project Edit View Display Tools Applications Workflows Scripts Help 2 3 t AT OT 96 0 pec 4E rV OU CORR Be Gi OWL ET N l Atoms 751 1081 Entries 1 2 Res 120 Chn 1 Mol 61 Chg 6 Jobs 0 0 middle xy rotate ctri middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu i Simulation Steps DE Shaw Research Prepare for simulation Prepare protein i E J En cu aT Att 4 1 IETA IM m 5 maestro 9
93. tralize Add cL Advanced ion placement Preparing a Desmond Simulation D E Shaw Research Generating the solvated system from command line lick the Write button in System Builder to save job files my setup mae is the Maestro structure file of the solute Serves as the input for system setup my setup csb is the command file an be hand edited for custom setup cases my setup out cms is the Maestro structure file of simulation system e Execute this command at the command line SSCHRODINGER run OSCHRODINGER utilities system builder my setup csb where my_setup is the file name given to the Write operation Preparing a Desmond Simulation DEShawR esearc h Setting up membrane systems e Embed a membrane protein structure in a membrane bilayer using the Setup Membrane panel An equilibrated membrane including accompanying water is used to generate a large enough region to encompass the protein Protein i positioned within the membrane using a semi automated procedure e Example uses the calcium ATPase protein 1su4 D E Shaw Research Membrane Systems Setting up membrane du hal maestro 9 0 109 Academic Use Only jujnyc kon sva EVA Maestro Project Edit View Disp Ies F alt flat t 3 FAT E D 3 b L C ton H s Au Il F ATOSA MPL RR E H H OH Operates on Workspace PDB 1su4 Diffraction data Browse
94. ualization and analysis using Maestro e Maestro offers basic visualization and analysis tools o Trajectory Player Similar to the ePlayer in the Project Table Designed to animate Desmond trajectories e Simulation Quality Analysis window Performs basic quality analysis Shows statistical properties of basic thermodynamic quantities based on block averages Schrodinger add on scripts Simulation Event Analysis Trajectory cluster analysis D E Shaw Research Visualization and Analysis Visualization and analysis using Maestro hal aestro 9 0 108 proj desres Desmond DropBox Desmond Tutorial 2 2 Tutorial 2 2 work Desmond job files Mee 3 Project Edit View Display Tools Applications Workflows Scripts Help 7 _ t ct do ow ES E i AZ HH H PERI tH Ay C 0 n i 1 E bw e IA H H Hn pope H aal INA a 2E Qe Es E un mM P KA wi a Ne si sia XYI Ae lt j lt j lt j OP q Atoms 0 0 Entries 0 0 5 0 Chn 0 Mol 0 Chg 0 Jobs 0 0 Commands middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold D D E Shaw Research Visualization and Analysis Visualization and analysis using Maestro H g H PECORE WU EU EI BEES HTH HL eH m H En fy LJ Lf WF ad
95. w Research Start Write Reset Close Help D E Shaw Research Free Energy Perturbation Preparing free energy perturbation 1 ipe hdd maestro 9 0 108 Academic Use Only proj desres Desmond DropBox Desmond_Tutorial_2 2 Tutorial_2 2_work Desmond_job_files 7 Maestro Project dit View Display Tools Applications Workflows Scripts Help 2 7 t H g 1 H DOE NEU Ae T 8 i g Cy Nos wy o Wi H H H bu A 0 Lt E d l T e X R ee Atoms 49 49 Entries 1 2 Res 1 Chn 1 Mol 1 Chg 5 Jobs 0 0 Commands j middle xy rotate ctrl middle z rotate right xy translate right click on atom spot center right click on atom bond and hold menu D E Shaw Research Preparing free energy perturbation Define Um Plan Stepl Display the ligand and its receptor if any in the Workspace Pick the attachment bond to define the core and the step 2 substitution group if Pick the attachment bond Step 3 Select fragments that will replace the substitution group Fragment library 9 items litem selected Select the fragment that will No Fragment Name View Reset replace the substitution group gt gt 953 UE ERREUR IE C For multiple fragments FEP creates different
96. when you launch Python others are loaded at runtime VMD provides built in modules for loading data into VMD querying and modifying VMD state molecule module atomsei module vmdnumpy module D E Shaw Research Visualization and Analysis Trajectory analysis with VMD Loading and viewing trajectories Structure files mae or cms Created by Maestro or Desmond Contain topology mass charge and possibly force field information e Single molecular system including solvent or ions Single snapshot of positions of atoms and virtual sites Select the Maestro mae file type to select these files Trajectory files dtr Created by Desmond Directory that contains metadata files and frame files holding snapshots e dtr files load positions dtrv files load positions and velocities Select the clickme dtr file D E Shaw Research Visualization and Analysis Trajectory analysis with VMD Loading files from the command line vmd mae structure cms dtr trajectory subdir clickme dtr his command reates a new molecule nitializes its structure from the cms file reates an initial set of coordinates from the cms file Appends all snapshots from the dtr file to the molecule Load multiple structure and trajectory files with m and f e m causes a new molecule to be created for each subsequent file e f causes subsequent files to be loaded into the same molecule v

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