March 2007 - modeller_usage

model ligand
by Bo Yang 31 Mar '07

31 Mar '07

Hello, Modeller: I try to model the ligand into my model by following the example of "Tutorial-2: Modeling ligands in the binding site'. First, I use a template and one of my model to build a alignment of the two. Then manually change the alignment to add "/.." to the end of the structures and sequence in the alignment. And change the number of residues of the structure file in the alignment. I then do the modeling using the modified alignment. But I keep getting the error message: modeller. error: check_a_337E> structure not read in I have checked that the structure files are all in the right path. I don't understand that why Modeller can't read the structure. I notice that the program generated two structure files ( all with xxx_fit) after the alignment. But these "xxx_fit" structures do not include the ligand. If I use these "xxx_fit" structures, there is no error message saying that "structure not read in", instead, it complain that "One or more atoms absent from MODEL". Since there is no ligand residue in such "xxx_fit" files. And if I manually add the ligand residue into the "xxx_fit", again, the modeller can't read the structure anymore. I have included the files used for modeling as attachments. I use mod 8v1. Thank you for help! Bo --------------------------------- Never miss an email again! Yahoo! Toolbar alerts you the instant new Mail arrives. Check it out. _aln.pos 10 20 30 40 50 60 1PQ2-2C8Ahem KLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKVYGPVFTVYFGMNPIVVFHGYEAVKEALIDNG 2c17mul1 ---------------------HMHNNFFKLQKKYGPIYSVRMGTKTTVIVGHHQLAKEVLI-KK 2c17 ---------------------HMHNNFFKLQKKYGPIYSVRMGTKTTVIVGHHQLAKEVLI-KK _consrvd * * *** * * * ** ** _aln.pos 70 80 90 100 110 120 1PQ2-2C8Ahem EEFSGRGN--SPISQRITKGLGIISSNG-KRWKEIRRFSL-TTLRNFGMGKRSIEDRVQEEAHC 2c17mul1 GKDFSGRPQMATLDIASNNRKGIAFADSGAHWQLHRRLAMATFALFKDGDQKLEKIICQEISTL 2c17 GKDFSGRPQMATLDIASNNRKGIAFADSGAHWQLHRRLAMATFALFKDGDQKLEKIICQEISTL _consrvd ** * ** * ** _aln.pos 130 140 150 160 170 180 190 1PQ2-2C8Ahem LVEELRKTKASPCDPTFILGCAPCNVICSVVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQV 2c17mul1 CDMLATHN-GQSIDISFPVFVAVTNVISLICFNTSYKN----GDPELNVIQNYNEGIID--NLS 2c17 CDMLATHN-GQSIDISFPVFVAVTNVISLICFNTSYKN----GDPELNVIQNYNEGIID--NLS _consrvd * * * *** * _aln.pos 200 210 220 230 240 250 1PQ2-2C8Ahem CNN------FPLLIDCFPGTHNKVLKNVALTRSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQ 2c17mul1 KDSLVDLVPWLKIFP--NKTLEKLKSHVKIRNDLLNKILENYKEKFRS-DSITNMLDTLMQAKM 2c17 KDSLVDLVPWLKIFP--NKTLEKLKSHVKIRNDLLNKILENYKEKFRS-DSITNMLDTLMQAKM _consrvd * * * * _aln.pos 260 270 280 290 300 310 320 1PQ2-2C8Ahem EKDNQKSEF-------NIENLVGTVADLFVAGTETTSTTLRYGLLLLLKHPEVTAKVQEEIDHV 2c17mul1 NSDNGNAGPDQDSELLSDNHILTTIGDIFGAGVETTTSVVKWTLAFLLHNPQVKKKLYEEIDQN 2c17 NSDNGNAGPDQDSELLSDNHILTTIGDIFGAGVETTTSVVKWTLAFLLHNPQVKKKLYEEIDQN _consrvd ** * * * ** *** * ** * * * **** _aln.pos 330 340 350 360 370 380 1PQ2-2C8Ahem IGRHRSPCMQDRSH-MPYTDAVVHEIQRYSDLVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTS 2c17mul1 VGFS-RTPTISDRNRLLLLEATIREVLRLRPVAPMLIPHKANVDSSIGEFAVDKGTEVIINLWA 2c17 VGFS-RTPTISDRNRLLLLEATIREVLRLRPVAPMLIPHKANVDSSIGEFAVDKGTEVIINLWA _consrvd * * * * * ** * *** * _aln.pos 390 400 410 420 430 440 1PQ2-2C8Ahem VLHDDKEFPNPNIFDPGHFLDKNGNFKKSD----YFMPFSAGKRICAGEGLARMELFLFLTTIL 2c17mul1 LHHNEKEWHQPDQFMPERFLN--PAGTQLISPSVSYLPFGAGPRSCIGEILARQELFLIMAWLL 2c17 LHHNEKEWHQPDQFMPERFLN--PAGTQLISPSVSYLPFGAGPRSCIGEILARQELFLIMAWLL _consrvd * ** * * * ** ** ** * * ** *** **** * _aln.pos 450 460 470 480 490 1PQ2-2C8Ahem QNFNLKSVDDLKNLNTTAVTKGIVSLPPSYQICFIPV-----/.. 2c17mul1 QRFDLEVPDDGQLPSLEGIP-KVVFLIDSFKVKIKVRQAWRE/-- 2c17 QRFDLEVPDDGQLPSLEGIP-KVVFLIDSFKVKIKVRQAWRE/.. _consrvd * * * ** * * *

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[Fwd: molecular dynamics simulations in modeller]
by Modeller Caretaker 29 Mar '07

29 Mar '07

-------- Original Message -------- Subject: molecular dynamics simulations in modeller Date: Wed, 28 Mar 2007 16:46:38 +0530 From: Archana Chavan <archananiper(a)gmail.com> To: modeller-care(a)salilab.org hello, can anybody tellm e more details about molecular dynamic simulations performed in modeller. i am using modeller 8v2 version on pentium IV workstation so how much time it may take to optimize the protein containing two chains, having length of 423 amino acid residues on the workstation i am using currently, and what is time requirement if i use SGI, IRIX 6.5 fuel work station for the same using default parameters in modeller? another thing i want to know is, which is the preferred method to obtain the best result after MD, whether i should go for the final model after all the steps of MD or the least energy model out of all the possible conformations it generated? -- Archana Chavan MS (Pharm)Pharmacoinformatics National Institute of Pharmaceutical Education and Research (NIPER) Mohali-160 062 Punjab, India. 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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Targeting Restraints for Weakening
by Brandon Mills 29 Mar '07

29 Mar '07

Hello all, I am generating models for a strained protein chimera using weakened restraints on one of the two domains, to see if Modeller will unfold the domain to relax the mechanical strain. I have weakened all Ca-Ca and N-O distance restraints (roughly 3,800 out of 16,500 total restraints) by a factor of 100, but it had nearly no effect on my output models. Is there something fundamentally flawed with this approach? Are there other specific restraints that might be recommended for weakening, or would it be best to simply weaken all restraints associated with the targeted domain? Thanks in advance! Sincerely, Brandon Mills -- Brandon Mills bmm25(a)pitt.edu (814) 360-1382 Lab: 338, Eberly Hall

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Quesion about patch the Terminal residues
by zhou jinming 27 Mar '07

27 Mar '07

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[Fwd: modeling crosslinked homodimeric protein]
by Modeller Caretaker 26 Mar '07

26 Mar '07

-------- Original Message -------- Subject: modeling crosslinked homodimeric protein Date: Mon, 26 Mar 2007 10:29:24 +0530 From: Archana Chavan <archananiper(a)gmail.com> To: modeller-care(a)salilab.org hello everybody, i am tryong to model the structure of enzyme which is crosslinked homodimeric protein two identical chains of protein are crosslinked in opposite orientation to form the two compete active sites. that is, both chains contribute fo the foramtion of aech of the active site. (there are 64 hydrogen bonds involved in inetaction between two chains) i tried to model to chains seperatly and superimpossed bsed on template, but the orientation of the chains is not giving the proper active site, so how i can model the whole protein, i.e. both the chains simultaneously so that i can get full active site? or is there any way by which seperatly modeled chaines can be put together? please suggest any solution for this problem. Thanks in advance. -- Archana Chavan MS (Pharm)Pharmacoinformatics National Institute of Pharmaceutical Education and Research (NIPER) Mohali-160 062 Punjab, India. phone:+91-(0)-9888847223 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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alignment of multiple templates
by Bo Yang 26 Mar '07

26 Mar '07

Hello, Modeller: I try to do a multiple structural alignment using the example of "salign.py" script. The command went through, but the alignment file only contained the last template sequence. I have attached my script and the alignment files generated. My pdb files containe only single chain. I can't figure out what could be wrong with my script. Why it always return the last template sequece. I use modeller 8v1. Thank you very much for your help! Bo --------------------------------- Bored stiff? Loosen up... Download and play hundreds of games for free on Yahoo! Games. log.verbose() env = environ() env.io.atom_files_directory = "./:../atom_files/" aln = alignment(env) for (code) in (('2HI4-1A2'), ('1PQ2-2C8A'), ('1OG5-2C9A')): mdl = model(env, file=code, model_segment=('FIRST:@', 'END:')) aln.append_model(mdl, atom_files=code, align_codes=code) for (weights, write_fit, whole) in (((1., 0., 0., 0., 1., 0.), False, True), ((1., 0.5, 1., 1., 1., 0.), False, True), ((1., 1., 1., 1., 1., 0.), True, False)): aln.salign(rms_cutoffs=(3.5, 6., 60, 60, 15, 60, 60, 60, 60, 60, 60), normalize_pp_scores=False, rr_file='$(LIB)/as1.sim.mat', overhang=30, gap_penalties_1d=(-450, -50), gap_penalties_3d=(0, 3), gap_gap_score=0, gap_residue_score=0, dendrogram_file='1is3A.tree', alignment_type='tree', # If 'progresive', the tree is not # computed and all structues will be # aligned sequentially to the first #ext_tree=True, # Tree building can be avoided if the tree # is input #input_weights_file='1is3A_exmat.mtx', feature_weights=weights, # For a multiple sequence alignment only # the first feature needs to be non-zero improve_alignment=True, fit=True, write_fit=write_fit, write_whole_pdb=whole, output='ALIGNMENT QUALITY') aln.write(file='test1a.pap', alignment_format='PAP') aln.write(file='test1a.ali', alignment_format='PIR') aln.salign(rms_cutoffs=(1.0, 6., 60, 60, 15, 60, 60, 60, 60, 60, 60), normalize_pp_scores=False, rr_file='$(LIB)/as1.sim.mat', overhang=30, gap_penalties_1d=(-450, -50), gap_penalties_3d=(0, 3), gap_gap_score=0, gap_residue_score=0, dendrogram_file='1is3A.tree', alignment_type='progressive', feature_weights=[0]*6, improve_alignment=False, fit=False, write_fit=True, write_whole_pdb=False, output='QUALITY') >P1;1OG5-2C9A structureX:1OG5-2C9A: 30 :A: 490 :A:undefined:undefined:-1.00:-1.00 PPGPTPLPVIGNILQIGIKDISKSLTNLSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAE RANRGFGIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVIC SIIFHKRFDYKDQQFLNLMEKLNENIEILSSPWIQVYNNFPALLDYFPGTHNKLLKNVAFMKSYILEKVKEHQES MDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIER VIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNP EMFDPHHFLDEGGNFKKSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASV PPFYQLCFIPV* _aln.pos 10 20 30 40 50 60 1OG5-2C9A PPGPTPLPVIGNILQIGIKDISKSLTNLSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSG _consrvd _aln.pos 70 80 90 100 110 120 130 1OG5-2C9A RGIFPLAERANRGFGIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASP _consrvd _aln.pos 140 150 160 170 180 190 200 1OG5-2C9A CDPTFILGCAPCNVICSIIFHKRFDYKDQQFLNLMEKLNENIEILSSPWIQVYNNFPALLDYFPGTH _consrvd _aln.pos 210 220 230 240 250 260 1OG5-2C9A NKLLKNVAFMKSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGA _consrvd _aln.po 270 280 290 300 310 320 330 1OG5-2C9A GTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPT _consrvd _aln.pos 340 350 360 370 380 390 400 1OG5-2C9A SLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFKKSKYFMPFSAG _consrvd _aln.pos 410 420 430 440 450 460 1OG5-2C9A KRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVPPFYQLCFIPV _consrvd

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changes in MODELLER9 optimization & DNA denaturation
by RYAN PAVLOVICZ 22 Mar '07

22 Mar '07

Hi. I just upgraded from MODELLER8v2 to 9v1 and am experiencing problems when modelling a protein-DNA complex in that the DNA is denaturing after optimization. When I use the same modelling script in 8v2, the DNA stays in its double-helical form, even when i use md_level= refine.very_slow. Can anyone explain to me what changes in the optimizers were made that cause this denaturation? I am using the MODELLER residue types ADE, GUA, CYT, and THY for the modelling. Thanks! ryan

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secondary structure assignment and patching
by Ryan 22 Mar '07

22 Mar '07

The template for one of my models has a large region in the middle of its sequence that shares no homology to my target sequence. Fortunately this region does not interact with the catalytic region in which I am interested, so I am able to remove this segment from the model. This means than my final model is composed of two chains. The problem I am having is with the secondary structure assignment to the second chain of the model. Without any explicit special secondary structure assignment the first chain of my model faithfully replicates the secondary structures of the template, while the second chain is lacking most if not all secondary structure. I know I could fix this problem by adding special restraints, but would rather have the model pick up secondary structure from the template. I am doing this modelling with default patching off. After a lot of testing, it seems that the N and C terminal patches are the cause of this loss in secondary structure to only the second chain of my model. If I comment out the patches to the protein termini but keep the patches I'm making to the DNA in my model, then I get the results I am looking for. Anyone have an idea why this is happening? Here is my input file: from modeller import * from modeller.automodel import * log.verbose() env = environ() env.patch_default = False env.io.hydrogen = env.io.hetatm = True env.io.atom_files_directory = './:~/homology' class mymodel(automodel): def special_patches(self, aln): self.patch(residue_type='5MC2', residues=(self.residues['253:C'])) self.patch(residue_type='DEO1', residues=(self.residues['248:C'])) ... self.patch(residue_type='5PHO', residues=(self.residues['248:C'])) self.patch(residue_type='5PHO', residues=(self.residues['260:D'])) # adjust 3' hydroxyl terminals of DNA strands self.patch(residue_type='3TER', residues=(self.residues['259:C'])) self.patch(residue_type='3TER', residues=(self.residues['271:D'])) # manually patch N termini self.patch(residue_type='NTER', residues=(self.residues['1:A'])) self.patch(residue_type='ACE ', residues=(self.residues['166:B'])) # manually patch C termini self.patch(residue_type='CTER', residues=(self.residues['165:A'])) self.patch(residue_type='CTER', residues=(self.residues['247:B'])) a = mymodel(env, alnfile = 'alignment.ali', knowns = ('template1','template2'), sequence = 'model3') a.starting_model= 1 a.ending_model = 1 a.make() I'd appreciate any help. Thanks! ryan

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HYP and alignment from other than modeller
by yuemin liu 21 Mar '07

21 Mar '07

Hi everyone, Is that possible to model HYP(Hydroxylproline) containing protein with PRO? I found HYP in the modeller lib, but no one-letter code for HYP. Another question is that how feasible is we use alignment from other program like blast when do modeling. Thanks, Liu, Yuemin ____________________________________________________________________________________ Bored stiff? Loosen up... Download and play hundreds of games for free on Yahoo! Games. http://games.yahoo.com/games/front

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how to select the best template?
by deepti 19 Mar '07

19 Mar '07

Dear modeller caretakers, please explain me the output of compare.py file,how to select the best template and what is Weighted pair-group average clustering based distance method? thanks and regards. --------------------------------------------------------------- Sequence identity comparison (ID_TABLE): Diagonal ... number of residues; Upper triangle ... number of identical residues; Lower triangle ... % sequence identity, id/min(length). 1uluA @11jw7A @12fhsA @1 1uluA @1 246 106 101 1jw7A @1 43 274 108 2fhsA @1 41 42 258 Weighted pair-group average clustering based on a distance matrix: .--- 1uluA @1.0 57.0000 | .---------------------------------------------------------- 1jw7A @1.0 58.5000 | .------------------------------------------------------------ 2fhsA @1.0 +----+----+----+----+----+----+----+----+----+----+----+----+ 58.5600 58.2900 58.0200 57.7500 57.4800 57.2100 56.9400 58.4250 58.1550 57.8850 57.6150 57.3450 57.0750

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