July 2007 - modeller_usage

modeller 9.2: spaghetti effect with multiple templates
by Raik Gruenberg 10 Aug '07

10 Aug '07

Hi modellers, already a while ago I have noticed that modeller tends to produce what I would call spaghetti proteins (containing knots and other fancy structures) when it is supplied with multiple templates that are far from the target (35 % or less) and also quite diverse among each other. However, Modeller 9 seems to suffer more from this effect than the previous versions: One of our test cases uses 10 templates with between 86% and 31% sequence similarity to the target. I know that this is not the optimal strategy (especially after reading this paper: http://bioinformatics.oxfordjournals.org/cgi/content/abstract/btm262v1 ) but modeller 8.2 still performed quite well and all 10 models had good topology (close to the 86% template) and secondary structure. However, I now re-run our test with modeller 9.1, using the identical alignment (T-Coffee) and the same input file (below) and the result looks much worse. Most among the 10 generated models show a messed up (swaped) topology, many have knots and the different models are generally more diverse. So to what extend differs the multiple-template treatment of Modeller 9 from previous versions? Do I need to use different parameters for multi-template modeling in the new version? Or is the general default modeling protocol different now? So here is our (old-style) input file: INCLUDE SET OUTPUT_CONTROL = 1 1 1 1 1 SET ALNFILE = 'final.pir_aln' SET KNOWNS = '1K2H_A' '1M31_A' '1J55_A' '1KSO_A' '1MQ1_A' '1MWN_A' '1MHO_' '1NSH_A' '1K8U_A' '1DT7_A' SET SEQUENCE = 'target' # code of the target SET ATOM_FILES_DIRECTORY = '../templates/modeller/' SET STARTING_MODEL= 1 # index of the first model SET ENDING_MODEL = 10 # index of the last model CALL ROUTINE = 'model' I am attaching a typical result of modeller 8 and one of modeller 9 for comparison. Thanks in advance for any comments! Best regards, Raik

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making a patch work
by Starr Hazard 10 Aug '07

10 Aug '07

Folks, I have created a RESI entry in top_heav.lib for a ligand of interest to me. When run without attempting to patch anything the RESI is accepted just fine and models are made with the appropriate ligand in an appropriate location. In reality the ligand forms a covalent bond with the protein. This is a Schiff Base linkage. My RESI is an aldehyde. The covalent bond is to the NZ of a lysine. I am deleting hydrogens from the LYS and the aldehyde oxygen from from the ligand to make the bond of interest to me. I created a PRES entry based on the disulfide example. PRES ELAZ +1.0000 ATOM 1:CE CT2 -0.10000 ATOM 1:NZ NN3 1.0000 ! trying to make a protonated Schiff base ATOM 2:C15 CN2 -0.08000 ATOM 2:C14 CT1 -0.10000 DELE ATOM 1:HZ3 DELE ATOM 1:HZ2 DELE ATOM 2:O32 BOND 1:NZ 2:C15 ANGL 1:CE 1:NZ 2:C15 1:NZ 2:C15 2:C14 DIHE 1:CD 1:CE 1:NZ 2:C15 1:NZ 2:C15 2:C14 2:C13 1:CE 1:NZ 2:C15 2:C14 IC 1:CD 1:CE 1:NZ 2:C15 0.0000 0.0000 92.5000 0.0000 0.0000 IC 1:CE 1:NZ 2:C15 2:C14 0.0000 0.0000 183.0000 0.0000 0.0000 IC 1:NZ 2:C15 2:C14 2:C13 0.0000 0.0000 177.0000 0.0000 0.0000 When I perform a test run of the code patch.py from the on-line manual (where I have added "env.io.hetatm=true" to read the ligand). The program appears to run but the log file shows numerous entries of this sort r_stere_607W > Cannot find parms in parm file Then remarks indicate that it has "added" some parms; so it gets past some instances where explicit information has not been supplied. It gets to a particular dihedral involving an atom that is supposed to be deleted by the patch ( see line above- 'DELE ATOM 2:O32' is the line in top.heav.lib; this is the aldehyde oxygen) and stops. The final line reads simply: FATAL error: assertion nbndpf < mbndpf failed in r_stereo.F90, line 608 At this point that error means absolutely nothing to me. The entries in the parm.lib file are often redundant for many entries. Are the columns described somewhere? Do I need to have explicit entries in the parm file for an atom that I hope to delete? I have not deciphered how to designate bond order in either the RESI entry or the PRES entry lines. How does one specify bond order? Starr

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Question about a protein structure
by Ester Fusté Domínguez 30 Jul '07

30 Jul '07

Dear sir/madam, I have a problem with modeller and probably you can help me. I want to do protein structure modelling. I have the sequence of a bacterium protein, and it's known that it has tree identical chains like this: MQMKKLFPIL IGLGLTGFSA MSQAENLLQV YQQARISNPD LRKSAADRDA AFEKINEARS PLLPQLGLGA DYTYTSGFRD YKDQNSNVTS GSLQLTQVLF DMSKWRALTL QEKQAGIQDV TYQTDQQTLI LNTATAYFKG LAAIDTLSYT EAQKQAIYRQ LDQTTQRFNV GLGAITDVQN ARSQYDAVLA NEVTARNDLD NAPQKLRQGT GNYYPELGSP NGKGFKTNKP QAVNALLKEA ESRNLSLLQA RLSQDLAREQ IPQAQDGHLP TLNLNASSGV SNNRYSGSKS ISQDADVGQN KIGLSFSLPL YQGGMVNSQV KQAQYNFVGA SEQLESAHRS VVQTVRSSFN NVNASISSIN AYKQAVVSAQ SSLDAMEAGY SVGTRTIVDV LDATTTLYNA KQQLSNARYN YLINELNIKS ALGTLNEQDL VALNNTLGKS IPTSPDSVAP ENPQQDASAD GYSNTAAAKP ASARTTQTSG SNPFRQ* I don't really know what can I do to avoid the chains overlap. I have tried to copy the sequence three times but it doesn't work. This is what I did: MQMKKLFPIL IGLGLTGFSA MSQAENLLQV YQQARISNPD LRKSAADRDA AFEKINEARS PLLPQLGLGA DYTYTSGFRD YKDQNSNVTS GSLQLTQVLF DMSKWRALTL QEKQAGIQDV TYQTDQQTLI LNTATAYFKG LAAIDTLSYT EAQKQAIYRQ LDQTTQRFNV GLGAITDVQN ARSQYDAVLA NEVTARNDLD NAPQKLRQGT GNYYPELGSP NGKGFKTNKP QAVNALLKEA ESRNLSLLQA RLSQDLAREQ IPQAQDGHLP TLNLNASSGV SNNRYSGSKS ISQDADVGQN KIGLSFSLPL YQGGMVNSQV KQAQYNFVGA SEQLESAHRS VVQTVRSSFN NVNASISSIN AYKQAVVSAQ SSLDAMEAGY SVGTRTIVDV LDATTTLYNA KQQLSNARYN YLINELNIKS ALGTLNEQDL VALNNTLGKS IPTSPDSVAP ENPQQDASAD GYSNTAAAKP ASARTTQTSG SNPFRQ MQMKKLFPIL IGLGLTGFSA MSQAENLLQV YQQARISNPD LRKSAADRDA AFEKINEARS PLLPQLGLGA DYTYTSGFRD YKDQNSNVTS GSLQLTQVLF DMSKWRALTL QEKQAGIQDV TYQTDQQTLI LNTATAYFKG LAAIDTLSYT EAQKQAIYRQ LDQTTQRFNV GLGAITDVQN ARSQYDAVLA NEVTARNDLD NAPQKLRQGT GNYYPELGSP NGKGFKTNKP QAVNALLKEA ESRNLSLLQA RLSQDLAREQ IPQAQDGHLP TLNLNASSGV SNNRYSGSKS ISQDADVGQN KIGLSFSLPL YQGGMVNSQV KQAQYNFVGA SEQLESAHRS VVQTVRSSFN NVNASISSIN AYKQAVVSAQ SSLDAMEAGY SVGTRTIVDV LDATTTLYNA KQQLSNARYN YLINELNIKS ALGTLNEQDL VALNNTLGKS IPTSPDSVAP ENPQQDASAD GYSNTAAAKP ASARTTQTSG SNPFRQ MQMKKLFPIL IGLGLTGFSA MSQAENLLQV YQQARISNPD LRKSAADRDA AFEKINEARS PLLPQLGLGA DYTYTSGFRD YKDQNSNVTS GSLQLTQVLF DMSKWRALTL QEKQAGIQDV TYQTDQQTLI LNTATAYFKG LAAIDTLSYT EAQKQAIYRQ LDQTTQRFNV GLGAITDVQN ARSQYDAVLA NEVTARNDLD NAPQKLRQGT GNYYPELGSP NGKGFKTNKP QAVNALLKEA ESRNLSLLQA RLSQDLAREQ IPQAQDGHLP TLNLNASSGV SNNRYSGSKS ISQDADVGQN KIGLSFSLPL YQGGMVNSQV KQAQYNFVGA SEQLESAHRS VVQTVRSSFN NVNASISSIN AYKQAVVSAQ SSLDAMEAGY SVGTRTIVDV LDATTTLYNA KQQLSNARYN YLINELNIKS ALGTLNEQDL VALNNTLGKS IPTSPDSVAP ENPQQDASAD GYSNTAAAKP ASARTTQTSG SNPFRQ* Could you help me, please? I need to know how can I find a solution and I don't know the way to get it. When I copy the sequence three times, the program don't distinguish the three chains, and it overlap them. I'm waiting for your reply. Thank you very much. Ester

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Block Ligand stereo chemistry problem
by Andre Fischer 26 Jul '07

26 Jul '07

Hi all, I am modelling a Protein with a ligand. The Ligand comes from the pdb template as a blk. Modeller works fine and the protein model seems reasonable, except that the modelled ligand is mirrored along its length axis compared to the template ligand. Also BLK Residues are defined rigid. some stereo operations seem to be allowed. How can i get rid of those? I want the ligand only to act as a steric constraint. Thank you very much Andre (Universität Regensburg, Germany)

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trouble modeling ligand
by Starr Hazard 18 Jul '07

18 Jul '07

Folks, Awhile back I wanted to get MODELLER 9v1 to place template water molecules into the modeled target sequences. I added "env.io.water = True" to my python script; then in the ali file _temp ERTF/wwwwwww _target ERTY/wwwwwww and incremented the indicated length in fields 3-6 of the structureX line to account for the waters. And all went well. Attempting to generalize to apply to a single ligand, I added "env.io.hetatm = True" to my python script and in the ali file _temp ERTF/. _target ERTY/. The HETATM entries for the ligand ARE in the template PDB file. Modeller refuses to run with this and in the log file it writes that the alignment and the PDB file have different lengths EVEN THOUGH I have incremented the actual length listed in the ALI file StructureX line in fields 3-6. In this particular case, the ligand in the template is covalently attached to a residue but I will want to model non-covalently bound ligands as well.

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DOPE score question
by hori koshii 17 Jul '07

17 Jul '07

Hi all, just a short question to make sure if: the assess_dope method in MODELLER accounts for all atoms when calculating the dope energy profile for each residue? (if so, do you know/think if DOPE may be more accurate than PROSA to some extent since the latter once take into account of the Calpha and/or Cb potential only) Thanks for answering. Good day/night! --------------------------------- Food fight? Enjoy some healthy debate in the Yahoo! Answers Food & Drink Q&A.

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disulphide
by Thijs Beuming 17 Jul '07

17 Jul '07

Hi, I have some problems making a disulphide bridge in MODELLER. Any help would be greatly appreciated. Thanks, Thijs Beuming My script: # Homology modeling by the automodel class from modeller import * # Load standard Modeller classes from modeller.automodel import * # Load the automodel class # Redefine the special_patches routine to include the additional disulfides # (this routine is empty by default): class mymodel(automodel): def special_patches(self, aln): # A disulfide between residues 176 and 185: self.patch(residue_type='DISU', residues=(self.residues['176'], self.residues ['185'])) log.verbose() # request verbose output env = environ() # create a new MODELLER environment to build this model in # directories for input atom files env.io.atom_files_directory = '~/NTProject2005/NEW_TCA/MODELLER' a = mymodel(env, alnfile = '~/NTProject2005/NEW_TCA/MODELLER/ molpharm.pir', # alignment filename knowns = '2A65-clean', # codes of the templates sequence = 'hNET') # code of the target a.starting_model= 1 # index of the first model a.ending_model = 1 # index of the last model # (determines how many models to calculate) a.make() # do the actual homology modeling The error: Traceback (most recent call last): File "model_hNET_xray2.py", line 26, in ? a.make() # do the actual homology modeling File "/softlib/exe/ia64/pkg/modeller/8v2/dist/modlib/modeller/ automodel/automodel.py", line 100, in make self.homcsr(exit_stage) File "/softlib/exe/ia64/pkg/modeller/8v2/dist/modlib/modeller/ automodel/automodel.py", line 334, in homcsr self.generate_method(self, aln) File "/softlib/exe/ia64/pkg/modeller/8v2/dist/modlib/modeller/ automodel/generate.py", line 24, in transfer_xyz mdl.create_topology(aln) File "/softlib/exe/ia64/pkg/modeller/8v2/dist/modlib/modeller/ automodel/automodel.py", line 483, in create_topology self.special_patches(aln) File "model_hNET_xray2.py", line 10, in special_patches self.patch(residue_type='DISU', residues=(self.residues['176'], File "/softlib/exe/ia64/pkg/modeller/8v2/dist/modlib/modeller/ model.py", line 543, in __getitem__ ret = modutil.handle_seq_indx(self, indx) File "/softlib/exe/ia64/pkg/modeller/8v2/dist/modlib/modeller/util/ modutil.py", line 117, in handle_seq_indx raise TypeError TypeError

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How to optimize a model
by Atila Iamarino 06 Jul '07

06 Jul '07

Dear Ben Webb, Thanks for everything you have been very helpful. I'm trying to include one model I generated in the optimization scrip fro FAQ: from modeller import * from modeller.automodel import * log.verbose() env = environ() a = automodel(env, alnfile='align1.ali', knowns='templ1', sequence='targ1') # Very thorough VTFM optimization: a.library_schedule = autosched.slow a.max_var_iterations = 300 # Very thorough MD optimization: a.md_level = refine.very_slow # Repeat the whole cycle 3-times and do not stop unless obj.func. > 1E6 a.repeat_optimization = 3 a.max_molpdf = 1e6 a.make() How can I do it? And how can I automate it including on this script to optimize only the best model: from modeller import * from modeller.automodel import * log.verbose() env = environ() a = automodel(env, alnfile = '1', knowns = ('2', '3'), sequence = 'bar', assess_methods=(assess.DOPE, assess.GA341)) a.starting_model= 1 a.ending_model = 10 a.make() # Get a list of all successfully built models from a.outputs ok_models = filter(lambda x: x['failure'] is None, a.outputs) # Rank the models by DOPE score key = 'DOPE score' ok_models.sort(lambda a,b: cmp(a[key], b[key])) # Get top model m = ok_models[0] print "Top model: %s (DOPE score %.3f)" % (m['name'], m[key]) a.make() Thanks again, -- Atila Iamarino L.E.M.B. - Laboratory of Molecular Evolution and Bioinformatics Av. Prof. Lineu Prestes, 1734 - USP (University of SÃ£o Paulo) - ICB Zip: 05508-000 Phone: +55 11 30917290 / +55 11 30918453

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pdb95.fsa
by Bo Yang 06 Jul '07

06 Jul '07

Hello, Modeller: I try to do a search for potentially related sequences of known structure by using the "build_profile.py" from the "command" section of Modeller9v1. But the program complaines that "Cannot open file pdb95.fsa: no such files". I search the Modeller9v1 package, and can't find the file named as "pdb95.fsa". Do you know where can I find the "pdb95.fsa" file? Or is there an alternative file that can be used as the "pdb95.fsa" in the program package? I notice that there is a file called "pdball.pir" from the download section of Modeller. Is this one can be used as a database? If so, how can I change the file format to .fsa? Thank you. I use modeller9v1. Bo --------------------------------- Looking for a deal? Find great prices on flights and hotels with Yahoo! FareChase.

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same values for the models 2
by Atila Iamarino 03 Jul '07

03 Jul '07

Dear Ben Webb, Do you have any example (.py file) of these changes, I can't find any on the examples that came with Modeller. Thanks! -- Atila Iamarino L.E.M.B. - Laboratory of Molecular Evolution and Bioinformatics Av. Prof. Lineu Prestes, 1734 - USP (University of SÃ£o Paulo) - ICB Zip: 05508-000 Phone: +55 11 30917290 / +55 11 30918453

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