Dear users,
I'm willing to create a peptide sequence from a fasta sequence, and add a disulfide bridge in it.
At the moment, my code "which works" is like this pseudo-code:
1 - create a model object, and model.build('sequence'), I am not applying any time of secondary structure constraint 2 - write this pdb (peptide.pdb) 3 - create a special align where target and template are identical (peptide.ali) 4 - create a new object, Mymodel derived from automodel to add the patch for disulfides 5 - generate models 6 - select the best one (peptide-cys.pdb)
I'm only willing to retrieve the "peptide-cys.pdb" file, can I bypass steps 2,3 and act directly on the initial model object created?
The implementation of the pseudo-code above is:
#####################################################################
# This demonstrates the use of alignment.append_sequence() and # model.build_sequence() to build residue sequences from one-letter codes # http://salilab.org/modeller/manual/node171.html
from modeller import * from modeller.automodel import *
env.libs.topology.read('${LIB}/top_heav.lib') env.libs.parameters.read('${LIB}/par.lib')
# Create a new empty alignment and model: aln = alignment(env) mdl = model(env)
mdl.build_sequence('ACAAAAACYAAAA') mdl.write(file='pept.pdb')
class MyModel(automodel): def special_patches(self, aln): # The disulfide bridge is taken from the input sequence self.patch(residue_type='DISU', residues=(self.residues['2', self.residues['8']))
a = MyModel(env, alnfile = "tmppiralign.ali", knowns = "pept", sequence = "pept-cys")
a.starting_model= 1 a.ending_model = 10
a.make()
#####################################################################
tmppiralign.ali is of the form:
##################################################################### >P1;pept structureX:pept:1: :13: :::: ACAAAAACYAAAA* >P1;pept-cys sequence:pept-cys::FIRST:@ END ::::: ACAAAAACYAAAA* #####################################################################
Thanks a lot for corrections, suggestions,..
Stéphane
On 11/25/2010 01:11 AM, Stéphane Téletchéa wrote: > I'm willing to create a peptide sequence from a fasta sequence, and add > a disulfide bridge in it. > > At the moment, my code "which works" is like this pseudo-code: > > 1 - create a model object, and model.build('sequence'), I am not > applying any time of secondary structure constraint > 2 - write this pdb (peptide.pdb) > 3 - create a special align where target and template are identical > (peptide.ali) > 4 - create a new object, Mymodel derived from automodel to add the patch > for disulfides > 5 - generate models > 6 - select the best one (peptide-cys.pdb)
That might work, although the restraints generated in step 4 would be all wrong (Modeller will be trying to make your models look like the extended chain you generated in step 1, but at the same time your disulfide patch will be trying to bring the pairs of CYS residues together). So even your best models will contain a *lot* of restraint violations.
Since you presumably have no structural information about your disulfide-bonded peptide, I would simply build the sequence in step 1 using model.build_sequence(): http://salilab.org/modeller/9v8/manual/node171.html
That function takes a special_patches argument, which is a user-provided function, so you can apply your DISU patches here.
Then I'd do some kind of optimization using simply stereochemical and van der Waals restraints, such as that at: http://salilab.org/modeller/9v8/manual/node253.html
Ben Webb, Modeller Caretaker
Modeller Caretaker a écrit : > On 11/25/2010 01:11 AM, Stéphane Téletchéa wrote: >> I'm willing to create a peptide sequence from a fasta sequence, and add >> a disulfide bridge in it. >> >> At the moment, my code "which works" is like this pseudo-code: >> >> 1 - create a model object, and model.build('sequence'), I am not >> applying any time of secondary structure constraint >> 2 - write this pdb (peptide.pdb) >> 3 - create a special align where target and template are identical >> (peptide.ali) >> 4 - create a new object, Mymodel derived from automodel to add the patch >> for disulfides >> 5 - generate models >> 6 - select the best one (peptide-cys.pdb) > > That might work, although the restraints generated in step 4 would be > all wrong (Modeller will be trying to make your models look like the > extended chain you generated in step 1, but at the same time your > disulfide patch will be trying to bring the pairs of CYS residues > together). So even your best models will contain a *lot* of restraint > violations. >
Indeed, the final pdf score is much better, and the structure seems more "reasonable".
I've incremented a little the examples you mentioned (I went there before posting but could not figure out out to call it, the "custom function" was the anwser...), using the approach for md as it is implemented in automodel.
So far, all went well, I'll use these peptides as starting points for the rest of my analysis.
Thanks a lot,
Stéphane
participants (2)
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Modeller Caretaker -
Stéphane Téletchéa