- modeller_usage - salilab.org

Regarding Salign
by Ashish Runthala 11 Jan '11

11 Jan '11

Dear Modellers, Will you please tell me how salign actually functions to compute "final max quality" produced for a considered set of templates. Thanks, Ashish Ashish Runthala, Lecturer, Structural Biology Cell, Biological Sciences Department, Faculty Division III, Birla Institute of Technology & Science - Pilani, INDIA

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Re: [modeller_usage] strategies for model refinement
by Mensur Dlakic 10 Jan '11

10 Jan '11

Thomas, I never really modeled a protein where loop conformation was crucial for the model itself, so I am usually content to refine the loops so they are stereochemically acceptable (I hope nobody reading this is cringing in horror at my relative indifference towards loop modeling). RAPPER for sure does a good job of improving Ramachandran outliers for loops up to 7-8 residues. The way it does it by "freezing" the protein outside of requested regions except for one "anchor" residue abutting the region and then samples the conformational space while making sure that rotamers with correct stereochemistry are utilized. I usually build 100 loops for each region and the program picks the one with lowest energy automatically, which is another reason I use it more than MODELLER for this purpose. For loops that are 6 or so residues, this takes less than two minutes. I would not try modeling loops that are 10+ residues, and in fact I usually omit them from my models if I have long insertions. Finally, these papers may (or may not, I haven't read them recently) offer the benchmark you were asking about: http://www.ncbi.nlm.nih.gov/pubmed/12596262 http://www.ncbi.nlm.nih.gov/pubmed/12596261 Best, Mensur At 07:14 PM 1/8/2011, Thomas Evangelidis wrote: >Mensur, are you aware of any benchmark analysis that shows RAPPER's >superiority on loop modeling over MODELLER? I am aware of one that >compares Rosetta, MODELLER and CABS on loops up to 24 aa if I remember >correctly, and shows that in short lengths all 3 programs are equivalent, >but for longer loops the combination of MODELLER with CABS prevails. > >I have several proteins with missing regions of varying length (8-47 aa) >which I want to fold. I have tried PyRosetta and MODELLER in the past but >I'm not impressed from the results of loop modeling, especially as the >length increases. I guess these routines were designed to model flexible >animo acid stretches that's why the predicted conformations adopt coiled >coils. To this end I also tried I-TASSER server (which employs Monte Carlo >with Replica Exchange for regions with no templates and is questionably >more accurate in folding long aa stretches) by supplying my initial >structure and excluding all homologues, but the meta-threading program >(LOMETS) it implements always detects traces of "homology" to some >irrelevant structures and uses them as templates. I guess my last resort >is MD with Replica Exchange but I haven't found the time yet to set up my >system and figure out a way to keep the rest of the model rigid, namely to >fold only the missing regions. > >This message is slightly off-topic, but I just wanted to share my >experience (and desperation) with other people that might find it helpful >(I hope not the desperation). > > >Thomas ========================================================================== | Mensur Dlakic, PhD | Tel: (406) 994-6576 | | Department of Microbiology | Fax: (406) 994-4926 | | Montana State University | | | 109 Lewis Hall, P.O. Box 173520 | http://myprofile.cos.com/mensur | | Bozeman, MT 59717-3520 | E-mail: mdlakic(a)montana.edu | ==========================================================================

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Re: [modeller_usage] model refinement
by Irene Newhouse 09 Jan '11

09 Jan '11

The discussion resulting from my question has been most interesting & most helpful! I'm saving it for future reference. The protein I'm working on almost has a missing loop - that is, someone finally managed to get crystals in which the previously missing residues were resolved. But someday, that won't be the case. I have a 2.33GHz linux box, and I started my 514-residue dimeric protein on Rosetta relax a short time after lunch on Friday. The job finished sometime Saturday night or the early hours of Sunday morning. The MolProbity score was 1.93. Thanks so much! Irene

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strategies for model refinement
by Irene Newhouse 08 Jan '11

08 Jan '11

I'm a relatively new user of modeller & successfully built a fairly nice model of a protein with 258 residues. It forms a homodimer, and has to be modeled as a dimer, because there's a very flexible loop that can easily adopt conformation that prevent dimerization if the 2nd unit isn't present. [I confirmed that by trying it]. Someone on this group suggested the Molprobity server as a way to assess model quality, for which I'm very grateful. He also suggested relaxing the structure with Rosetta, & after epic battles with python setup & my operating system, I got it up & running. Only to learn from the RosettaCommons forum that Rosetta relax doesn't scale well with chain length & isn't useful for proteins with >200 residues. I managed to get the Molprobity score down to a respectable 2.-something using lots & lots of iterations of Schrodinger Prime loop refinement & side chain minimization. It took about a week of setting up a loop, running it, checking to see if it refined, iterating 'til I could move on, etc. So I'm looking for something a bit less hands-on, if possible. Also, Schrodinger is expensive & my boss may not renew the licenses when this lot expires in March. And finally, Molprobity signaled several C-beta issues in my structure, & Schrodinger just doesn't seem to do much about those. Therefore, I'm looking for other suggestions, preferably freeware, for model refinement. I have tried some loop refinement with Modeller itself, but wasn't thrilled with the outcome. This could easily be because I couldn't find sample scripts to copy, or an explanation of how to tweak the parameters if the loop doesn't seem to be refining. If anyone can point me in those directions, I'd be grateful, too. Thanks so much!

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cyclic peptide modeling
by r.yu＠imb.uq.edu.au 05 Jan '11

05 Jan '11

Dear Users, I want to use modeller to model the cyclopeptide. Before sending question here, I checked the mail-list and found other people had asked similar questions. However, when I tried to solve my own problem based on the suggestion, I still could not get my problem resolved. I have attached the script as following: # Homology modeling by the automodel class from modeller.automodel import * # Load standard Modeller classes env = environ() # create a new MODELLER environment to build this model in # directories for input atom files env.io.atom_files_directory = '/home/rileiyu/model/single/atom' # Disable default NTER and CTER patching env.patch_default=False class mymodel(automodel): def special_patches(self, aln): # Link between residues 22 and 1 to make chain cyclic: self.patch(residue_type='LINK', residue_ids=('22:', '1:')) a = mymodel(env, alnfile = 'single', # alignment filename knowns = 'mii', # codes of the templates sequence = 'cmii',) # code of the target a.make() # do the actual homology modeling But when I started to model my cyclopepetide the problem appeared as: Traceback (most recent call last): File "model.py", line 21, in ? a.make() # do the actual homology modeling File "/home/rileiyu/share/modeller9v7/modlib/modeller/automodel/automodel.py", line 98, in make self.homcsr(exit_stage) File "/home/rileiyu/share/modeller9v7/modlib/modeller/automodel/automodel.py", line 427, in homcsr self.make_initial_model(aln) File "/home/rileiyu/share/modeller9v7/modlib/modeller/automodel/automodel.py", line 441, in make_initial_model self.generate_method(self, aln) File "/home/rileiyu/share/modeller9v7/modlib/modeller/automodel/generate.py", line 25, in transfer_xyz mdl.create_topology(aln) File "/home/rileiyu/share/modeller9v7/modlib/modeller/automodel/automodel.py", line 659, in create_topology self.special_patches(aln) File "model.py", line 13, in special_patches self.patch(residue_type='LINK', residue_ids=('22:', '1:')) TypeError: patch() got an unexpected keyword argument 'residue_ids' Can anyone here give me more suggestions please? Very appreciated for your help!

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problem in doing difficuly modeling using modeller 9v8
by ranu sharma 27 Dec '10

27 Dec '10

Hello Sir/Madam, Good Afternoon. I am facing problem while doing Difficult modelling for my protein. It is showing the following error. I am attaching the .aln file, my .pdb and model.py file for your reference. Hope to get a reply from you soon. Thanks & Regards. *ERROR:* C:\Program Files\Modeller9v8\examples\ranu_basic\C4H>mod9v8 model.py 'import site' failed; use -v for traceback Traceback (most recent call last): File "model.py", line 9, in ? a.make() File "C:\Program Files\Modeller9v8\modlib\modeller\automodel\automodel.py", li ne 98, in make self.homcsr(exit_stage) File "C:\Program Files\Modeller9v8\modlib\modeller\automodel\automodel.py", li ne 424, in homcsr self.check_alignment(aln) File "C:\Program Files\Modeller9v8\modlib\modeller\automodel\automodel.py", li ne 406, in check_alignment aln.check() File "C:\Program Files\Modeller9v8\modlib\modeller\alignment.py", line 200, in check self.check_structure_structure(io=io) File "C:\Program Files\Modeller9v8\modlib\modeller\alignment.py", line 209, in check_structure_structure return f(self.modpt, io.modpt, self.env.libs.modpt, eqvdst) _modeller.ModellerError: check_a_282E> Unable to read structural information for alignment sequence: 1 2fdvA This command requires structures. -- Ranu Sharma Msc Bioinformatics, Pune University JRF, National Chemical Laboratory, Pune -- Ranu Sharma Msc Bioinformatics, Pune University JRF, National Chemical Laboratory, Pune -- Ranu Sharma Msc Bioinformatics, Pune University JRF, National Chemical Laboratory, Pune

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Quiero ser tu amigo en Quepasa.com
by Sergio Garay 27 Dec '10

27 Dec '10

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Re: [modeller_usage] modeller_usage Digest, Vol 9, Issue 130
by Ashish Runthala 26 Dec '10

26 Dec '10

What is the length of the target protein, which you are calling a Difficult one. Your aln file is not found. Attach your align2d.py or salign.py respectively, if you are using single or multiple templates for modeling. Also attach your target sequence target.seq file. Good Luck, Ashish Ashish Runthala, Lecturer, Structural Biology Cell, Biological Sciences Group, Birla Institute of Technology & Science, Pilani, Rajasthan - 333031 From: ranu sharma <ranusharma09(a)gmail.com> Subject: [modeller_usage] problem in doing difficuly modeling using modeller 9v8 To: modeller_usage(a)salilab.org Message-ID: <AANLkTikhoQUvqSQA1GkKauo9=XctiXy2v27mX-LWrtYZ(a)mail.gmail.com> Content-Type: text/plain; charset="iso-8859-1" Hello Sir/Madam, Good Afternoon. I am facing problem while doing Difficult modelling for my protein. It is showing the following error. I am attaching the .aln file, my .pdb and model.py file for your reference. Hope to get a reply from you soon. Thanks & Regards. *ERROR:* C:\Program Files\Modeller9v8\examples\ranu_basic\C4H>mod9v8 model.py 'import site' failed; use -v for traceback Traceback (most recent call last): File "model.py", line 9, in ? a.make() File "C:\Program Files\Modeller9v8\modlib\modeller\automodel\automodel.py", li ne 98, in make self.homcsr(exit_stage) File "C:\Program Files\Modeller9v8\modlib\modeller\automodel\automodel.py", li ne 424, in homcsr self.check_alignment(aln) File "C:\Program Files\Modeller9v8\modlib\modeller\automodel\automodel.py", li ne 406, in check_alignment aln.check() File "C:\Program Files\Modeller9v8\modlib\modeller\alignment.py", line 200, in check self.check_structure_structure(io=io) File "C:\Program Files\Modeller9v8\modlib\modeller\alignment.py", line 209, in check_structure_structure return f(self.modpt, io.modpt, self.env.libs.modpt, eqvdst) _modeller.ModellerError: check_a_282E> Unable to read structural information for alignment sequence: 1 2fdvA This command requires structures. -- Ranu Sharma Msc Bioinformatics, Pune University JRF, National Chemical Laboratory, Pune -- Ranu Sharma Msc Bioinformatics, Pune University JRF, National Chemical Laboratory, Pune -- Ranu Sharma Msc Bioinformatics, Pune University JRF, National Chemical Laboratory, Pune

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Re: [modeller_usage] DOPE and sequence/model length (Modeller Caretaker)
by MUSTAFA BUGHIO 26 Dec '10

26 Dec '10

On Sat, Dec 25, 2010 at 11:30 PM, <modeller_usage-request(a)salilab.org>wrote: > Send modeller_usage mailing list submissions to > modeller_usage(a)salilab.org > > To subscribe or unsubscribe via the World Wide Web, visit > https://salilab.org/mailman/listinfo/modeller_usage > or, via email, send a message with subject or body 'help' to > modeller_usage-request(a)salilab.org > > You can reach the person managing the list at > modeller_usage-owner(a)salilab.org > > When replying, please edit your Subject line so it is more specific > than "Re: Contents of modeller_usage digest..." > > > Today's Topics: > > 1. Re: modified amino acids (Modeller Caretaker) > 2. DOPE and sequence/model length (Starr Hazard) > 3. Re: DOPE and sequence/model length (Modeller Caretaker) > 4. problem in doing difficuly modeling using modeller 9v8 > (ranu sharma) > > > ---------------------------------------------------------------------- > > Message: 1 > Date: Thu, 16 Dec 2010 10:09:27 -0800 > From: Modeller Caretaker <modeller-care(a)salilab.org> > Subject: Re: [modeller_usage] modified amino acids > To: Mike White <mwhite(a)drexelmed.edu> > Cc: ModellerUsage List List <modeller_usage(a)salilab.org> > Message-ID: <4D0A55D7.9050204(a)salilab.org> > Content-Type: text/plain; charset=ISO-8859-1; format=flowed > > On 12/16/10 6:04 AM, Mike White wrote: > > I am trying to model a small (22 amino acids) peptide with 3 > > disulfide bonds using structures of 6 related peptides with Modeller > > 9.7. The template peptides have 1-3 modified amino acids > > (pyroglutamate, hydroxyproline, amidated C-termini) and the peptide > > to be modeled has an amidated cysteine as the C-terminus. > > Modeller cannot build models containing modified amino acids, nor can it > use structural information from modified amino acids in your templates > (the only exception is MSE, which Modeller treats as identical to MET). > > Your best option in this case is to edit your template PDB file to > convert the modified amino acids to their unmodified equivalents, build > models with regular cysteine, and modify the C-terminus of the > constructed models. > > > I tried setting env.io.hetatm= True to see if that made a difference, > > but then the routine failed with the following track back: > ... > > I'm not sure why env.io.hetatm = 'True' causes this error > > True and 'True' are two different things. True is a Python boolean; > 'True' is a string. Only the first will work here. > > Ben Webb, Modeller Caretaker > -- > modeller-care(a)salilab.org http://www.salilab.org/modeller/ > Modeller mail list: http://salilab.org/mailman/listinfo/modeller_usage > > > ------------------------------ > > Message: 2 > Date: Thu, 16 Dec 2010 14:51:44 -0500 > From: Starr Hazard <hazards(a)musc.edu> > Subject: [modeller_usage] DOPE and sequence/model length > To: modeller_usage(a)salilab.org > Message-ID: <4D0A6DD0.2000407(a)musc.edu> > Content-Type: text/plain; charset=ISO-8859-1; format=flowed > > Folks, > > I have modeled some dimers of a large protein and a much shorter partner > (~350aa for X and about 80aa for Y) . There are crystal templates for > such dimers. The best resolution structures have different large and > small proteins. So I have templates with X'Y' and X''Y''. X' and X'' > are homologs as are Y' and Y''. The Y family is quite variable in > length. When homologs from distant organisms ( eg plant, fungi, fish > mammal) are aligned there are gaps compared to the mammalian templates. > > In mammals X' and X'' are in related but distinct clades. If I model a > yeast X protein to each mammalian template can I say that the yeast > protein is better represented by one or the other template based on a > DOPE score? ( the GA341 scores are not helpful since they are always > 1.000 for these models) > > This is several questions I guess. 1) Are DOPE energies normally > distributed? > Could I > statistically compare DOPE scores of models made with one template to > those from another template. > 2) I have > some evidence that longer XY pairs have "better" DOPE scores than > shorter pairs. Is there a statistical way to control for "length"? > 3) I was > just looking at DOPE scores for two models. One with from an alignment > with gaps and the other from an alignment without gaps. > The PDB > model files are different sizes yet the scores are identical. Does DOPE > ignore regions that are not in the template? > > Starr > > > ------------------------------ > > Message: 3 > Date: Mon, 20 Dec 2010 17:01:01 -0800 > From: Modeller Caretaker <modeller-care(a)salilab.org> > Subject: Re: [modeller_usage] DOPE and sequence/model length > To: Starr Hazard <hazards(a)musc.edu> > Cc: modeller_usage(a)salilab.org > Message-ID: <4D0FFC4D.2060005(a)salilab.org> > Content-Type: text/plain; charset=ISO-8859-1; format=flowed > > On 12/16/2010 11:51 AM, Starr Hazard wrote: > > This is several questions I guess. 1) Are DOPE energies normally > > distributed? Could I statistically compare DOPE scores of models made > > with one template to those from another template. > > DOPE is a sum of individual energies over all pairs of atoms in your > final model - it does not include any information from the template or > modeling process. So you can compare DOPE scores for two models of the > same sequence, regardless of their source. > > > 2) I have some evidence that longer XY pairs have "better" DOPE > > scores than shorter pairs. Is there a statistical way to control for > > "length"? > > You can't compare these directly. Use the normalized DOPE score instead, > which *is* corrected for length (it is a z score). > > > 3) I was just looking at DOPE scores for two models. One with from an > > alignment with gaps and the other from an alignment without gaps. > > The PDB model files are different sizes yet the scores are identical. > > Does DOPE ignore regions that are not in the template? > > Yes. See (1) above. > > Ben Webb, Modeller Caretaker > -- > modeller-care(a)salilab.org http://www.salilab.org/modeller/ > Modeller mail list: http://salilab.org/mailman/listinfo/modeller_usage > > > ------------------------------ > > Message: 4 > Date: Sun, 26 Dec 2010 13:00:39 +0530 > From: ranu sharma <ranusharma09(a)gmail.com> > Subject: [modeller_usage] problem in doing difficuly modeling using > modeller 9v8 > To: modeller_usage(a)salilab.org > Message-ID: > <AANLkTikhoQUvqSQA1GkKauo9=XctiXy2v27mX-LWrtYZ(a)mail.gmail.com> > Content-Type: text/plain; charset="iso-8859-1" > > Hello Sir/Madam, > > Good Afternoon. I am facing problem while doing Difficult modelling for my > protein. It is showing the following error. > I am attaching the .aln file, my .pdb and model.py file for your reference. > Hope to get a reply from you soon. > > > > > > Thanks & Regards. > > > *ERROR:* > > C:\Program Files\Modeller9v8\examples\ranu_basic\C4H>mod9v8 model.py > 'import site' failed; use -v for traceback > Traceback (most recent call last): > File "model.py", line 9, in ? > a.make() > File "C:\Program > Files\Modeller9v8\modlib\modeller\automodel\automodel.py", li > ne 98, in make > self.homcsr(exit_stage) > File "C:\Program > Files\Modeller9v8\modlib\modeller\automodel\automodel.py", li > ne 424, in homcsr > self.check_alignment(aln) > File "C:\Program > Files\Modeller9v8\modlib\modeller\automodel\automodel.py", li > ne 406, in check_alignment > aln.check() > File "C:\Program Files\Modeller9v8\modlib\modeller\alignment.py", line > 200, in > check > self.check_structure_structure(io=io) > File "C:\Program Files\Modeller9v8\modlib\modeller\alignment.py", line > 209, in > check_structure_structure > return f(self.modpt, io.modpt, self.env.libs.modpt, eqvdst) > _modeller.ModellerError: check_a_282E> Unable to read structural > information > for > alignment sequence: 1 2fdvA This command requires structures. > > > > > > > > -- > Ranu Sharma > Msc Bioinformatics, Pune University > JRF, National Chemical Laboratory, Pune > > > > -- > Ranu Sharma > Msc Bioinformatics, Pune University > JRF, National Chemical Laboratory, Pune > > > > -- > Ranu Sharma > Msc Bioinformatics, Pune University > JRF, National Chemical Laboratory, Pune >

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DOPE and sequence/model length
by Starr Hazard 20 Dec '10

20 Dec '10

Folks, I have modeled some dimers of a large protein and a much shorter partner (~350aa for X and about 80aa for Y) . There are crystal templates for such dimers. The best resolution structures have different large and small proteins. So I have templates with X'Y' and X''Y''. X' and X'' are homologs as are Y' and Y''. The Y family is quite variable in length. When homologs from distant organisms ( eg plant, fungi, fish mammal) are aligned there are gaps compared to the mammalian templates. In mammals X' and X'' are in related but distinct clades. If I model a yeast X protein to each mammalian template can I say that the yeast protein is better represented by one or the other template based on a DOPE score? ( the GA341 scores are not helpful since they are always 1.000 for these models) This is several questions I guess. 1) Are DOPE energies normally distributed? Could I statistically compare DOPE scores of models made with one template to those from another template. 2) I have some evidence that longer XY pairs have "better" DOPE scores than shorter pairs. Is there a statistical way to control for "length"? 3) I was just looking at DOPE scores for two models. One with from an alignment with gaps and the other from an alignment without gaps. The PDB model files are different sizes yet the scores are identical. Does DOPE ignore regions that are not in the template? Starr

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