- modeller_usage - salilab.org

Heterodimer modeling
by Xiongzhuo Gao 11 Jun '12

11 Jun '12

Dear Modellers, I'm building a heterodimer with a homodimer template. I have the template pdb file (dimer.pdb) and the sequence file of the heterodimer (hetero.ali). Here is the hetero.ali file: >P1;hetero sequence:to_model:1:A:859:B:853::: AAAAAAAAAAAAAAAAAAAAA/BBBBBBBBBBBBBBBBB There are 859 a.a. in one chain and 853 a.a. in the other chain. I didn't type the exact number of a.a. here. The following is the script I used for alignment: from modeller import * env = environ() aln = alignment(env) mdl = model(env, file='dimer', model_segment=('FIRST:A','LAST:A')) aln.append_model(mdl, align_codes='dimerAB', atom_files='dimer.pdb') # I used "dimerAB" to point out both chain A and chain B for alignment. I don't know whether it is correct. aln.append(file='hetero.ali', align_codes='hetero') aln.align2d() aln.write(file='hetero-dimerAB.ali', alignment_format='PIR') aln.write(file='hetero-dimerAB.pap', alignment_format='PAP') The script running result showed the two chain of the heterodimer aligned to one chain of the template. Would you kindly tell me how I can get the correct alignment? Thank you. Xiongzhuo Gao BMCB Department University of New Hampshier Durham, New Hampshire 03824

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Chimeric protein - residue numbers
by Larsson, Per (pl6n) 05 Jun '12

05 Jun '12

Hi! I am trying to build a model using the automodel class, based on two known structures where I want parts of the model to be based on structure A and parts on structure B. My alignment file looks like this: >P1;protein_a structureX:protein_a:1::238::::: aaaaaaaaaa---------aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa------------------aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa--------------------------aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa-----------------------aaaaaaaaaaaaaaaa---------* >P1;protein_b structureX:protein_b:1::93::::: ----------bbbbbbbbb-----------------------------------bbbbbbbbbbbbbbbbbb-------------------------------------------bbbbbbbbbbbbbbbbbbbbbbbbbb-------------------------------------------------bbbbbbbbbbbbbbbbbbbbbbb----------------bbbbbbbb* >P1;chimera sequence:chimera:1::238::::: aaaaaaaaabbbbbbbbbbaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaabbbbbbbbbbbbbbbbbbbaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaabbbbbbbbbbbbbbbbbbbbbbbbbbaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaabbbbbbbbbbbbbbbbbbbbbbbaaaaaaaaaaaaaaaabbbbbbb* In my structure files, protein_a contains residues from 1-238. The residues in protein_b are a subset of the residues in protein_a, but I want restraints to be derived from protein_b for some parts of the final model. When running this in Modeller (v 9.10) i get the error read_te_291E> Sequence difference between alignment and pdb : x (mismatch at alignment position 11) which I believe comes from the fact that since protein_a contains all residues, Modeller does not skip residues in the protein_a file, and a mismatch occurs. Do I need to remove residues from the structure in protein_a, or is there some way to tell Modeller to skip those residues when matching the sequence of residues in the structure file with the sequence of residues in the alignment file? Or alternatively tell Modeller to use restraints from only protein_b for parts of the model? Thanks /Per Larsson

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Chimeric alignment - residue numbers
by Larsson, Per (pl6n) 05 Jun '12

05 Jun '12

Hi! I am trying to build a model using the automodel class, based on two known structures where I want parts of the model to be based on structure A and parts on structure B. My alignment file looks like this: >P1;protein_a structureX:protein_a:1::238::::: aaaaaaaaaa---------aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa------------------aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa--------------------------aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa-----------------------aaaaaaaaaaaaaaaa---------* >P1;protein_b structureX:protein_b:1::93::::: ----------bbbbbbbbb-----------------------------------bbbbbbbbbbbbbbbbbb-------------------------------------------bbbbbbbbbbbbbbbbbbbbbbbbbb-------------------------------------------------bbbbbbbbbbbbbbbbbbbbbbb----------------bbbbbbbb* >P1;chimera sequence:chimera:1::238::::: aaaaaaaaabbbbbbbbbbaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaabbbbbbbbbbbbbbbbbbbaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaabbbbbbbbbbbbbbbbbbbbbbbbbbaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaabbbbbbbbbbbbbbbbbbbbbbbaaaaaaaaaaaaaaaabbbbbbb* In my structure files, protein_a contains residues from 1-238. The residues in protein_b are a subset of the residues in protein_a, but I want restraints to be derived from protein_b for some parts of the final model. When running this in Modeller (v 9.10) i get the error read_te_291E> Sequence difference between alignment and pdb : x (mismatch at alignment position 11) which I believe comes from the fact that since protein_a contains all residues, Modeller does not skip residues in the protein_a file, and a mismatch occurs. Do I need to remove residues from the structure in protein_a, or is there some way to tell Modeller to skip those residues when matching the sequence of residues in the structure file with the sequence of residues in the alignment file? Or alternatively tell Modeller to use restraints from only protein_b for parts of the model? Thanks /Per Larsosn

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Invitation to connect on LinkedIn
by Arvind Pal via LinkedIn 04 Jun '12

04 Jun '12

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signal peptide structure modeling
by Kwee Hong 31 May '12

31 May '12

Hi, I would like to model signal peptide structure. I would like to know is this possible with MODELLER? Or is there any relevant modeling server? Thanks, Joyce

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Re: [modeller_usage] PD: Re: optimization schedule
by M 31 May '12

31 May '12

Thank you very much, that was exacly what I wanted to know. Sorry for my poor description of those problems. > On 5/31/12 11:06 AM, M wrote: > > Thank you very much. One last question: how are the atoms (residues) > > chosen for individual CG step? For example if residue span range is > > 10, does it mean that only first residues are optimized? > > I don't know what you mean by "first residues" here. The schedule isn't > for picking which atoms are optimized (that is the job of the selection > - see automodel's select_atoms method - which by default is all atoms). > The schedule picks which *restraints* are optimized. If the span range > is 10, that means all atom-atom restraints that act on atoms in residues > at most 10 apart in sequence are optimized. > > Ben Webb, Modeller Caretaker > -- > modeller-care(a)salilab.org http://www.salilab.org/modeller/ > Modeller mail list: http://salilab.org/mailman/listinfo/modeller_usage

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Re: [modeller_usage] PD: Re: optimization schedule
by M 31 May '12

31 May '12

Thank you very much. One last question: how are the atoms (residues) chosen for individual CG step? For example if residue span range is 10, does it mean that only first residues are optimized? > On 5/31/12 10:26 AM, M wrote: > > I was asking about the Conjugate gradients optimization > > initializations (each step of adding additional restraints), not > > about the steps of one CG process. > > Before the schedule is used in comparative modeling, schedule steps with > a range larger than the length of your sequence are removed, since they > are redundant; see > http://salilab.org/modeller/9.10/manual/node267.html > > Ben Webb, Modeller Caretaker > -- > modeller-care(a)salilab.org http://www.salilab.org/modeller/ > Modeller mail list: http://salilab.org/mailman/listinfo/modeller_usage

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PD: Re: optimization schedule
by M 31 May '12

31 May '12

I don;t think I specified the problem well. This is a part of the output: # Conjugate gradients optimization # Step Current energy Av shift Mx shift Funcs Gradient 0 127763.69531 0.0000 0.0000 1 5.80191e+06 9 1023.20831 0.0001 0.0013 27 7958.03 # Conjugate gradients optimization # Step Current energy Av shift Mx shift Funcs Gradient 0 10585.82617 0.0000 0.0000 1 798323 10 3038.98022 0.0422 0.5213 21 44036.2 20 1562.34656 0.0573 0.4620 41 21124.6 30 952.08020 0.0387 0.3051 61 6975.25 40 718.60651 0.0190 0.1223 81 2768.92 50 613.78882 0.0165 0.1318 101 1072.04 60 558.44568 0.0191 0.1931 121 844.107 70 528.58771 0.0160 0.1610 142 623.547 80 505.49722 0.0071 0.0432 162 182.543 90 488.25266 0.0116 0.0833 182 371.858 100 472.90448 0.0159 0.2190 202 199.59 110 464.42642 0.0060 0.0553 222 123.018 120 459.06067 0.0065 0.0453 242 74.0072 127 456.91678 0.0008 0.0088 258 27.1187 # Conjugate gradients optimization # Step Current energy Av shift Mx shift Funcs Gradient 0 2565.44043 0.0000 0.0000 1 872.504 1 2564.90918 0.0005 0.0043 3 776.596 # Conjugate gradients optimization (...) I was asking about the Conjugate gradients optimization initializations (each step of adding additional restraints), not about the steps of one CG process. slow = schedule(4, [ step(CG, 2, mk_scale(default=0.01, nonbond=0.0)), step(CG, 4, mk_scale(default=0.10, nonbond=0.0)), step(CG, 6, mk_scale(default=0.50, nonbond=0.0)) ] + \ [ step(CG, rng, mk_scale(default=1.00, nonbond=0.0)) for rng in \ (8,10,14,18,20,24,30,25,40,45,50,55,60,70,80,90,100,120,140,160,200, 250,300,400,500) ] + \ [ step(CG, 600, mk_scale(default=1.00, nonbond=0.01)), step(CG, 800, mk_scale(default=1.00, nonbond=0.1)), step(CG, 1000, mk_scale(default=1.00, nonbond=0.5)), step(CG, 9999, physical.values(default=1.00)) ]) Number of steps from the script above is 32 (I understand, that those are the steps of each CG initializations), while CG initializations is smaller. I'm not asking about for example 9 steps of individual CG process from the top of the encolsed log fragment. Dnia 31-05-2012 o godz. 19:17 Modeller Caretaker <modeller-care(a)salilab.org> napisał(a): > On 5/31/12 9:53 AM, M wrote: > > While analysing the log file of the optimization proces (X.D00000001) > > I've discovered, that the number of steps is different than the > > number from the applied schedule. What is the cause? > > See http://salilab.org/modeller/9.10/manual/node258.html, in particular > the description of the min_atom_shift parameter. > > Ben Webb, Modeller Caretaker > -- > modeller-care(a)salilab.org http://www.salilab.org/modeller/ > Modeller mail list: http://salilab.org/mailman/listinfo/modeller_usage

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optimization schedule
by M 31 May '12

31 May '12

Hello, While analysing the log file of the optimization proces (X.D00000001) I've discovered, that the number of steps is different than the number from the applied schedule. What is the cause? The script I have used: from modeller import * from modeller.automodel import * env = environ() env.schedule_scale = physical.values(default=1.0, soft_sphere=0.7) log.level(output=1, notes=1, warnings=1, errors=1, memory=0) a = automodel(env, alnfile='alignment.pir', knowns='template', sequence='target', assess_methods=(assess.DOPE, assess.GA341)) a.starting_model = 1 a.ending_model = 200 a.library_schedule = autosched.slow a.max_var_iterations = 300 a.md_level = refine.slow a.repeat_optimization = 3 a.max_molpdf = 1e6 a.make() The autosched.slow schedule according to the file from the modeller folder consists of 32 CG steps, while the log file contains only 27 steps per iteration.

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short interatomic distances
by M 29 May '12

29 May '12

Hello, I have a problem concerning the step of evaluating my model. I'm using the whatif server (http://swift.cmbi.ru.nl/servers/html/index.html) Most of the scores are fine, but there are many abnormally short interatomic distances according to whatif. The problem doesn't result from the alignment. Is it possible that it is a result of different parametrization used by modeller (or by the implemented CHARMM force field)? Below is an enclosed example of the whatif log file concerning the short distances (two columns from the end with numbers are important: the first number in the table tells how much shorter that specific contact is than the acceptable limit, the second distance is the distance between the centres of the two atoms): 15 ILE ( 15-) A CG2 <-> 59 MET ( 59-) A SD 0.33 3.07 INTRA BF 179 MET ( 179-) A SD <-> 207 VAL ( 207-) B CG1 0.31 3.09 INTRA BL 19 THR ( 19-) A N <-> 252 LEU ( 252-) B CD2 0.28 2.82 INTRA BF 19 THR ( 19-) A CG2 <-> 55 ALA ( 55-) A CB 0.27 2.93 INTRA BF 154 VAL ( 154-) A CG2 <-> 156 LEU ( 156-) A CD2 0.27 2.93 INTRA BF 217 PHE ( 217-) B CE1 <-> 244 LEU ( 244-) B CD2 0.27 2.93 INTRA BF 105 TYR ( 105-) A CA <-> 186 ILE ( 186-) A CD1 0.27 2.93 INTRA BF 138 THR ( 138-) A CG2 <-> 139 LEU ( 139-) A CD1 0.26 2.94 INTRA BF 258 TYR ( 258-) B CB <-> 265 LEU ( 265-) B CD1 0.26 2.94 INTRA BF 19 THR ( 19-) A CB <-> 252 LEU ( 252-) B CD2 0.26 2.94 INTRA BF 65 THR ( 65-) A CG2 <-> 72 TRP ( 72-) A CE3 0.26 2.94 INTRA BF 179 MET ( 179-) A CE <-> 207 VAL ( 207-) B CG1 0.25 2.95 INTRA BL 239 VAL ( 239-) B CG1 <-> 243 PHE ( 243-) B CE2 0.25 2.95 INTRA BF 256 PHE ( 256-) B CE2 <-> 260 PHE ( 260-) B CZ 0.25 2.95 INTRA BF 220 LEU ( 220-) B CD1 <-> 235 ILE ( 235-) B CG1 0.25 2.95 INTRA BF 73 ILE ( 73-) A CD1 <-> 74 PHE ( 74-) A CD1 0.25 2.95 INTRA BF 33 VAL ( 33-) A CG1 <-> 35 LYS ( 35-) A CG 0.25 2.95 INTRA BL 25 LEU ( 25-) A CD2 <-> 269 TYR ( 269-) B CD1 0.25 2.95 INTRA BL 65 THR ( 65-) A CG2 <-> 72 TRP ( 72-) A CZ3 0.25 2.95 INTRA BF this is not a full list (fortunately other values are better, deviation from the acceptable value is small). Best regards, Mat

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