March 2011 - modeller_usage

modelling from 2 templates, one for major part of sequence, 1 for insertion region
by Irene Newhouse 21 Mar '11

21 Mar '11

I'm trying to model a protein that looks like a member of CIS_IPPS with reasonable homlogy for a major portion of the sequence, but with a significant insertion region that has weak homology to a portion of a different protein. I tried to build with the .py & .ali files listed below, with the result that the CIS_IPPS regions of the protein were built just fine, but the insertion region was nothing but a random coil. When I extracted the insertion region & modeled it based on the extracted portion of the other protein, I was able to model something reasonable. I could use a GUI to meld the two models together, but I'd rather have recommendations as to how to get modeller to do the build for me - I think it'd be a lot better starting structure than the result of a hand-meld. Thanks in advance! Irene Newhouse .py file: from modeller import * # Load standard Modeller classes from modeller.automodel import * # Load the automodel class log.verbose() # request verbose output # Override the 'special_restraints' and 'user_after_single_model' methods: class MyModel(automodel): def special_restraints(self, aln): # Constrain the A and B chains to be identical (but only restrain # the C-alpha atoms, to reduce the number of interatomic distances # that need to be calculated): s1 = selection(self.chains['A']).only_atom_types('CA') s2 = selection(self.chains['B']).only_atom_types('CA') self.restraints.symmetry.append(symmetry(s1, s2, 1.0)) def user_after_single_model(self): # Report on symmetry violations greater than 1A after building # each model: self.restraints.symmetry.report(1.0) env = environ() # create a new MODELLER environment to build this model in # directories for input atom files env.io.atom_files_directory = ['.', '/home/newhoir/rubber/'] #read HETATMS in template env.io.hetatm = True # Be sure to use 'MyModel' rather than 'automodel' here! a = MyModel(env, alnfile = 'rub4b.ali' , # alignment filename knowns = ('2x06', '2erx'), # codes of the templates sequence = '1cp4', # code of the target assess_methods=assess.GA341) # request model assessment a.starting_model= 1 # index of the first model a.ending_model = 20 # index of the last model # (determines how many models to calculate) a.library_schedule = autosched.slow # thorough VTFM opt a.max_var_iterations = 300 a.md_level = refine.very_slow a.make() # do the actual homology modeling The .ali file: >P1;2x06 structureX:2x06:12:A:+474:B:PDB::0.00:0.00 -------------------------KLPAHG--CRHVAIIMDGNGRWAKKQGKIRAFGHKAGAKSVRRAVSFAANNGIEALTLYAFSSENWNRPAQEVSALMELFVWALDSEVKS---LHRHNVRLRIIGDTSRFNSRLQERIRKSEALTAGNTGLTLNIAANYGGRWDIVQGVR--------------------------------------------------------------QLAEKVQQGNLQPDQIDEEMLN-----------------------------------------------QHVCMHELAPVDLVIRTGGEHRISNFLLWQIAYAELYFTDVLWPDFDEQDFEGALNAFANRE----------.../-------------------------KLPAHG--CRHVAIIMDGNGRWAKKQGKIRAFGHKAGAKSVRRAVSFAANNGIEALTLYAFSSENWNRPAQEVSALMELFVWALDSEVKS---LHRHNVRLRIIGDTSRFNSRLQERIRKSEALTAGNTGLTLNIAANYGGRWDIVQGVR--------------------------------------------------------------QLAEKVQQGNLQPDQIDEEMLN-----------------------------------------------QHVCMHELAPVDLVIRTGGEHRISNFLLWQIAYAELYFTDVLWPDFDEQDFEGALNAFANRE----------...* >P1;2erx structureX:2erx:16:A:+66:B:PDB::0.00:0.00 ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------GGVGKSSLVLRFVKGTFRESYIPTVEDTYRQVI------------------------------------------------------------------------------------------------------/---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------GGVGKSSLVLRFVKGTFRESYIPTVEDTYRQVI------------------------------------------------------------------------------------------------------* >P1;1cp4 sequence:1cp4:1:A:+758:B:::0.00:0.00 MGKHSSSRVSELFGNLGSFIRACIFRVLSMGPIPNHFAFIMDGNRRYAKKENMKKGAGHRAGFLALISILKYCYELGVKYVTIYAFSIDNFKRNPDEVKDLMDLMLEKIEELLRDESIVNQYGIRVYFIGNLKLLSEPVRIAAEKVMRATAKNTNCTLLICIAYTSRDEIVHAVQGSCKNKREDILPLSFCKANNGDIEEVEDDKKVHGVSPFVFSESQKDEAGESQATIASVTCSCLARGVEGGGNKNSMVVRAVRGSYEDKW-----DNYQAVMENRTGSGVTPSEENKNMQGECSIVKLVDIEKQMYMAVAPEPDILIRSSGESRLSNFLLWQSSECLLYSPDALWPEIGLWHLVWAVLNFQRNHSYLERKKHQL.../MGKHSSSRVSELFGNLGSFIRACIFRVLSMGPIPNHFAFIMDGNRRYAKKENMKKGAGHRAGFLALISILKYCYELGVKYVTIYAFSIDNFKRNPDEVKDLMDLMLEKIEELLRDESIVNQYGIRVYFIGNLKLLSEPVRIAAEKVMRATAKNTNCTLLICIAYTSRDEIVHAVQGSCKNKREDILPLSFCKANNGDIEEVEDDKKVHGVSPFVFSESQKDEAGESQATIASVTCSCLARGVEGGGNKNSMVVRAVRGSYEDKW-----DNYQAVMENRTGSGVTPSEENKNMQGECSIVKLVDIEKQMYMAVAPEPDILIRSSGESRLSNFLLWQSSECLLYSPDALWPEIGLWHLVWAVLNFQRNHSYLERKKHQL...*

2 1

Modeller and Fedora 14 / python 2.7
by Susan Hutchinson 21 Mar '11

21 Mar '11

I wonder if anyone could help, please. After upgrading our systems from Fedora 12 to Fedora 14 we are unable to run modeller. It installs but fails to run, reporting the following errors: Traceback (most recent call last): File "modeller_gi60681617.py", line 2, in<module> from modeller import * # Load standard Modeller classes File "/usr/lib64/python2.7/site-packages/modeller/__init__.py", line 72, in<module> import _modeller ImportError: No module named _modeller Do you know of any problems with Modeller and recent versions of Fedora? Can you confirm that Modeller will work with Python 2.7 - the version that runs on Fedora 14 systems. The package is essential for one of our research groups and I would be very grateful for any help or advice you can give me. Many thanks, Susan Hutchinson -- Susan Hutchinson hutchins(a)stats.ox.ac.uk Computing Support Specialist http://www.stats.ox.ac.uk Department of Statistics Tel : +44 (0)1865 282852 1 South Parks Road, Fax : +44 (0)1865 272595 Oxford OX1 3TG, UK.

3 4

NaN error model generation Lennard-Jones restraints
by David Rodríguez 18 Mar '11

18 Mar '11

Hi, In order to obtain models with less clashes (and improved stereochemistry) as measured by Molprobity, I followed this thread: http://salilab.org/archives/modeller_usage/2010/msg00382.html Taking Nick's advice into account, I switched on the dynamic Lennard-Jones restraints with the simple script shown below. Some models are generated, showing improved statistics regarding clashes and stereochemical quality, but many others fail to be generated due to NaN values in the optimization process (see 'yyyy.D00000002' file attached), and shown in the .log file as: ... yyyy.B99990002.pdb Obj. func. (nan) exceeded max_molpdf (10000000.000) ... I have varied many variables (different alignments, targets, using optimization values as in the 'model_changeopt.py' example script...), but the problem remains. The .ini file looks fine, and of course switching off LJ restraints does not yied that error. I hope someone would help with this issue. Thanks in advance. Regards, -- automodel_lj.py -- # Homology modeling by the automodel class from modeller import * # Load standard Modeller classes from modeller.automodel import * # Load the automodel class 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 = ['./'] energy_data.dynamic_lennard = True a = automodel(env, alnfile = 'file.ali', # alignment filename knowns = 'xxxx', # codes of the templates sequence = 'yyyy', # code of the target assess_methods=(assess.DOPE, assess.GA341)) a.starting_model= 1 # index of the first model a.ending_model = 15 # index of the last model # (determines how many models to calculate) ## Very thorough VTFM optimization: #a.library_schedule = autosched.slow #a.max_var_iterations = 300 ## Very thorough MD optimization: #a.md_level = refine.very_slow a.make() # do the actual homology modeling -- David Rodríguez Díaz, PhD Student Fundación Pública Galega de Medicina Xenómica (SERGAS) Santiago de Compostela (Spain) http://webspersoais.usc.es/persoais/david.rodriguez.diaz <http://webspersoais.usc.es/persoais/david.rodriguez.diaz>

2 1

E-values for profile building
by Lilit Nersisyan 18 Mar '11

18 Mar '11

I have a question regarding the e-values used in the build_profile. When I set the e-value less then 6, no sequences are found, but for higher e-values (with high numbers of iterations) several sequences are found that have e-values less than 1. What is the reason? Thank you. -- Lilit Nersisyan Institute of Molecular Biology NAS RA E-mail: txgt.lilit.nersisyan(a)gmail.com Tel.: +37494 601703

2 1

Fedora 14 and Modeller
by flavio seixas 18 Mar '11

18 Mar '11

Hi, I was trying to install modeller on an AMD AthlonX2 Fedora-14 Linux machine 64-bit x86_64 RPM version. The following error message appears: [root@NIR Downloads]# env KEY_MODELLER9v8=<my password> rpm -Uvh modeller-9v8-1.x86_64.rpm warning: modeller-9v8-1.x86_64.rpm: Header V4 DSA/SHA1 Signature, key ID 745e6093: NOKEY Preparing... ########################################### [100%] 1:modeller ########################################### [100%] restorecon reset /usr/lib/modeller9v8/lib/x86_64-intel8/libifcore.so.5 context system_u:object_r:lib_t:s0->system_u:object_r:textrel_shlib_t:s0 [root@NIR Downloads]# I tested typing: [root@NIR Downloads]# mod9v8 /usr/lib/modeller9v8/bin/mod9v8_x86_64-intel8: error while loading shared libraries: libintlc.so.5: cannot enable executable stack as shared object requires: Permission denied Is there any library missing? I did not found nothing related with libifcore or libintlc at google... Thanks for any help. Flavio

2 1

licence key for using modellar
by An＠mIk＠ SiNgH 15 Mar '11

15 Mar '11

please provide me the to get licence key for using modellar.... -- **Anamika Singh

2 1

Re: [modeller_usage] Beta strand
by Thomas Evangelidis 09 Mar '11

09 Mar '11

On 9 March 2011 15:44, Claudia Scotti <claudiascotti(a)hotmail.com> wrote: > Dear Thomas, > > Many thanks for your suggestions. > > Yes: I have already tried to remove the alignment, but the "strand" does > not become a strand and it moves away from the beta sheet against which it > is supposed to pack. > > Mmhhh... Actually, should I try the beta sheet restraints? In this case, > please, I have some doubts on the command: > It would be a good idea to try both the strand and beta sheet restraints and the leave this region unaligned. > > rsr.add(secondary_structure.sheet(at['N:1'], at['O:14'],sheet_h_bonds=-5)) > > Particuarly, please, I can't find the explanation of the syntax in > parenthesis. May you please help me with this? > You mean the hydrogen bonding pattern in a beta sheet? Here is an explanation: http://en.wikipedia.org/wiki/Beta_sheet#Hydrogen_bonding_patterns and this one from Modeller's manual: http://www.salilab.org/modeller/manual/node219.html This is an example code snippet from my archive: rsr.add(secondary_structure.strand(self.residue_range('1:', '7:'))) rsr.add(secondary_structure.strand(self.residue_range('19:', '26:'))) rsr.add(secondary_structure.strand(self.residue_range('56:', '63:'))) ##An anti-parallel sheet composed of the two strands: self.restraints.add(secondary_structure.sheet(at['N:2'], at['O:23'], sheet_h_bonds=-12)) self.restraints.add(secondary_structure.sheet(at['O:1'], at['N:59'], sheet_h_bonds=-8)) Good luck! Thomas -- ====================================================================== Thomas Evangelidis PhD student Biomedical Research Foundation, Academy of Athens 4 Soranou Ephessiou , 115 27 Athens, Greece email: tevang(a)bioacademy.gr tevang3(a)gmail.com website: https://sites.google.com/site/thomasevangelidishomepage/

1 0

Beta strand
by Claudia Scotti 09 Mar '11

09 Mar '11

Dear All, Please, I cannot model a beta strand (predicted as such by PSI PRED) in a protein model, even adding further restraints. I think this depends on the fact that this region is not structured in the templates. Please, any suggestions (see .py below)? Many thanks. Claudia ------- # Homology modeling with multiple templates from modeller import * # Load standard Modeller classes from modeller.automodel import * # Load the automodel class 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 = ['.', '../atom_files'] class MyModel(automodel): def special_restraints(self, aln): rsr = self.restraints at = self.atoms # unpick('1:', '73:') # condense('1:', '73:') # Add some restraints from a file: # rsr.append(file='my_rsrs1.rsr') # Residues 49 through 55 should be an alpha helix: rsr.add(secondary_structure.alpha(self.residue_range('39:', '45:'))) # Two beta-strands: # rsr.add(secondary_structure.strand(self.residue_range('1:', '5:'))) # rsr.add(secondary_structure.strand(self.residue_range('19:', '26:'))) # rsr.add(secondary_structure.strand(self.residue_range('33:', '35:'))) # rsr.add(secondary_structure.strand(self.residue_range('55:', '58:'))) rsr.add(secondary_structure.strand(self.residue_range('68:', '72:'))) # An anti-parallel sheet composed of the two strands: # rsr.add(secondary_structure.sheet(at['N:1'], at['O:14'], # sheet_h_bonds=-5)) # Use the following instead for a *parallel* sheet: # rsr.add(secondary_structure.sheet(at['N:1'], at['O:9'], # sheet_h_bonds=5)) # Restrain the specified CA-CA distance to 10 angstroms (st. dev.=0.1) # Use a harmonic potential and X-Y distance group. # rsr.add(forms.gaussian(group=physical.xy_distance, # feature=features.distance(at['CA:35'], # at['CA:40']), # mean=10.0, stdev=0.1)) a = MyModel(env, alnfile = 'Alignment2.ali', # alignment filename knowns = ('pco','Tas','gen','Rap'), # codes of the templates sequence = 'sALK1') # code of the target a.starting_model= 1 # index of the first model a.ending_model = 10 # index of the last model # (determines how many models to calculate) a.make() # do the actual homology modeling -- Claudia Scotti, MD PhD Department of Experimental Medicine University of Pavia Via Ferrata, 1 27100 Pavia Italy Tel. 0382 986335 Facs 0382 986893 Claudia Scotti Dipartimento di Medicina Sperimentale Sezione di Patologia Generale Universita' di Pavia Via Ferrata, 1 27100 Pavia Italia Tel. 0039 0382 986335/8/1 Facs 0039 0382 303673

2 1

problem of build_profile
by Bishwajit Das 07 Mar '11

07 Mar '11

When i run this program showing an error from modeller import * log.verbose() env = environ() #-- Prepare the input files #-- Read in the sequence database sdb = sequence_db(env) sdb.read(seq_database_file='pdb95.fsa', seq_database_format='FASTA', chains_list='ALL', minmax_db_seq_len=(1, 40000), clean_sequences=True) #-- Write the sequence database in binary form sdb.write(seq_database_file='pdb95.bin', seq_database_format='BINARY', chains_list='ALL') #-- Now, read in the binary database sdb.read(seq_database_file='pdb95.bin', seq_database_format='BINARY', chains_list='ALL') #-- Read in the target sequence/alignment aln = alignment(env) aln.append(file='toxin.ali', alignment_format='PIR', align_codes='ALL') #-- Convert the input sequence/alignment into # profile format prf = aln.to_profile() #-- Scan sequence database to pick up homologous sequences prf.build(sdb, matrix_offset=-450, rr_file='${LIB}/blosum62.sim.mat', gap_penalties_1d=(-500, -50), n_prof_iterations=5, check_profile=False, max_aln_evalue=0.01, gaps_in_target=False) #-- Write out the profile prf.write(file='buildprofile.prf', profile_format='TEXT') #-- Convert the profile back to alignment format aln = prf.to_alignment() #-- Write out the alignment file aln.write(file='buildprofile.ali', alignment_format='PIR') could not open the file pdb_95.fsa where i get this file?? -- * BISHWAJIT DAS* *+91-9433237920* KOLKATA

2 1

about random seeds
by albert 06 Mar '11

06 Mar '11

Hello: I am using the random seeds when I building model these days. and I found that in the following line: environ(rand_seed=-8123, restyp_lib_file='$(LIB)/restyp.lib', copy=None) I try three jobs with rand_sees=-500, -1000, -1500 and I found that the -1500 get the lowest DOPE score and -500 get the highest DOPE score for the best solution. Does it means that if I set rand_sees=-2000 would get a better one? Thank you very much

2 1