- modeller_usage - salilab.org

Reconstruction of CA position only files with all-atom template
by jingkaizeng 13 Nov '24

13 Nov '24

Hi all, Here is my task: I have some CA position only files of a protein of interested that underlying some important biological pathways. We also have the protein full Cryo-EM structures (pdb:8io4, the exact same protein as well as sequence as the CA only files). Then I would like to fill the keep the CA position only files' CA position (don't move at all) then reconstruct the detail like side chain/secondary structure information from template. So this task is not homology modeling but reconstruction. After getting the reconstructed files, I would like to use these into MD simulations. I searched from previous mail list, and I found one did this task but not based on template. https://www.salilab.org/archives/modeller_usage/2008/msg00285.html I tried with " env = Environ() # Load the CA-only seed model seed_model = Model(env, file=seed_file) # Load the template structure (with full atomistic detail) template_model = Model(env, file=template_file) # Create an alignment between the seed and itself (1:1 alignment) aln = Alignment(env) aln.append_model(seed_model, align_codes='seed') aln.append_model(seed_model, align_codes='seed') # Write the alignment for debugging purposes aln.write(file='alignment.ali', alignment_format='PIR') # Define a custom model class to fix the Cα positions class MyModel(automodel): def select_atoms(self): # Select all atoms except the Cα atoms to allow refinement of everything but Cα s = selection(self) return s - s.only_atom_types('CA') # Set up environment for refinement env.edat.nonbonded_sel_atoms = 2 # Disable interactions between selected and unselected atoms a = MyModel(env, alnfile = aln, # Alignment file created earlier knowns = 'seed', # Seed model (CA-only) sequence = 'seed') # Target is also the seed (1:1 alignment) a.starting_model = 1 a.ending_model = 1 a.make() " But this code didn't use the side chain atom from the Cryo-EM structure, and just use CA position to reconstruct the detail. It seems the reconstruction by this code is not reliable enough that cause infinite energy error in MD simulation, it may indicate some overlap or incorrect side-chain orientations, or improper hydrogen placements. Therefore, I would need to try to reconstruct with the side chain information from template Cryo-EM structure's pdb. I tried some methods that use the template Cryo-EM structure, but it seems we just do the homology modeling but NOT reconstruction. The production files we get is almost same as the template without make use of the CA position from CA only files. The code I used like : " # Load the CA-only seed model seed_model = Model(env, file=seed_file) # Load the template structure (with full atomistic detail) template_model = Model(env, file=template_file) # Create an alignment between the seed and the template aln = Alignment(env) aln.append_model(template_model, align_codes='template') aln.append_model(seed_model, align_codes='seed') # Perform the alignment aln.align() # Now defining a custom AutoModel class to apply Cα restraints class MyModel(AutoModel): def special_restraints(self, aln): # Restrain all Cα atoms based on the seed model rsr = self.restraints atmsel = selection(self).only_atom_types('CA') # Apply restraints to the selected Cα atoms for atom in atmsel: rsr.add(forms.Gaussian(group=physical.xy_distance, feature=features.Distance(atom, atom), mean=0.0, # No change in CA positions stdev=0.01)) # Instantiate the custom model class a = MyModel(env, alnfile=aln, knowns='template', sequence='seed') a.starting_model = 1 a.ending_model = 1 a.make() " I think this task can be done since I found a paper (https://doi.org/10.7554/eLife.68369) that do the similar task, they claim to use Modeller to perform this: "First, side chain atoms from the template X-ray structure (PDB ID 4HFI) were added to each model, followed by a cycle of refinement with all Ca atoms restrained. Restraints on Ca atoms were then substituted with restraints on backbone hydrogen bonds, taken from helix and sheet annotations in the template PDB file, for another cycle of refinement to ensure proper secondary structure." Can anyone give some suggestions about this reconstruction task? Thanks. Best, Jingkai

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Missing residues modeling in Modeller
by bbmpresi＠gmail.com 04 Nov '24

04 Nov '24

Dear all, I am trying to model the missing residues in a beta barrel shaped protein that contains 12 missing residues in the original pdb. As instructed for the 1qg8 tutorial, I also first obtained the full amino acid sequence of the protein using: from modeller import * # Get the sequence of the 1qg8 PDB file, and write to an alignment file code = 'pdbid' e = Environ() m = Model(e, file=code) aln = Alignment(e) aln.append_model(m, align_codes=code) aln.write(file=code+'.seq') and I am obtaining an output file named pdbid.seq The actual protein sequence contains 324 amino acid residues and 12 residues are missing in the pdbid.pdb file This is the alignment.ali file I am preparing for missing residue addition: >P1;pdbid structureX:pdbid:1:A:+312:A:MOL_ID 1; ASDQRGYKP------------GGHVGTSVEYEDKVTRGFNNTDKKEKTITNEVFNFFYNNPQWNFMGFYSFKIENREQKEPGYYENEDGIKQLFSLNKGHDLGNGWATGLIYELEYTRSKVYSPDVSGLRKNLAEHSIRPYLTYWNNDYNMGFYSNLEYLLSKEDRNAWGKRQEQGYSALFKPYKRFGNWEVGVEFYYQIKTNDEKQPDGTINEKSDFNERYIEPIVQYSFDDAGTLYTRVRVGKNETKNTDRSGGGNAGINYFKDIRKATVGYEQSIGESWVAKAEYEYANEVEKKSRLSGWEARNKSELTQHTFYAQALYRF* >P1;pdb_fill sequence::::::::: ASDQRGYKPEDVAFDESFFSFGGHVGTSVEYEDKVTRGFNNTDKKEKTITNEVFNFFYNNPQWNFMGFYSFKIENREQKEPGYYENEDGIKQLFSLNKGHDLGNGWATGLIYELEYTRSKVYSPDVSGLRKNLAEHSIRPYLTYWNNDYNMGFYSNLEYLLSKEDRNAWGKRQEQGYSALFKPYKRFGNWEVGVEFYYQIKTNDEKQPDGTINEKSDFNERYIEPIVQYSFDDAGTLYTRVRVGKNETKNTDRSGGGNAGINYFKDIRKATVGYEQSIGESWVAKAEYEYANEVEKKSRLSGWEARNKSELTQHTFYAQALYRF* But in the template I get residue number written as 312 instead of 324, I directly copied the entry from the pdbid.seq file that was provided by Modeller at the first step that I explained at the beginning. Due to 12 missing residues Modeller is reporting 312 residues in the second line of the alignment.ali file: structureX:pdbid:1:A:+312:A:MOL_ID 1; However, I checked other examples on Modeller tutorial and it seems in some examples the total residue numbers (including the missing residue numbers) are written in the template section for the alignment.ali file, so I could have used structureX:pdbid:1:A:+324:A:MOL_ID 1; writing 324 as total number of residues for the template; so my question is that does it matter if write structureX:pdbid:1:A:+312:A:MOL_ID 1; or structureX:pdbid:1:A:+324:A:MOL_ID 1; I generated a new pdb with all missing residues modelled by Modeller using: from modeller import * from modeller.automodel import * # Load the AutoModel class log.verbose() env = Environ() # directories for input atom files env.io.atom_files_directory = ['.', '../atom_files'] class MyModel(AutoModel): def select_atoms(self): return Selection(self.residue_range('10:A', '21:A')) #a = MyModel(env, alnfile = 'alignment.ali', # knowns = 'pdbid', sequence = 'pdbid_fill') a = AutoModel(env, alnfile = 'alignment.ali', knowns = 'pdbid', sequence = 'pdbid_fill') a.starting_model= 1 a.ending_model = 5 a.make() I checked that using structureX:pdbid:1:A:+312:A:MOL_ID 1; or structureX:pdbid:1:A:+324:A:MOL_ID 1; in the second line of alignment.ali for the template, I am obtaining a very similar or more or less identical modeled structure. Can anybody tell me if the number of residues written in the second line of alignment.ali file for template pdb matters or not? Or only the template sequence and the gaps really matter? Any help would be much appreciated, thank you

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Fwd: Average the models
by Marco Sette 24 Oct '24

24 Oct '24

Thanks Ben, is there a way to avoid that an insertion from becoming a curious loop like the one shown at the top in the figure? I’m trying to relax the system using MD but maybe I can avoid it during modeling. Best, Marco Il 22/10/2024 01:26, Modeller Caretaker ha scritto: > On 10/21/24 2:28 AM, Marco Sette via modeller_usage wrote: >> I have obtained five models of a protein with Modeller and I am >> analyzing them in relation to the wt. There are of course small >> deviations, and such differences affect some physical properties. In >> your opinion, should I analyze the separate models or I can take the >> average structure? In NMR, people often use an average structure so I >> wonder if it makes sense in the modelling field. > > Normally we look at the individual models. If you do want to average > the structures, I would recommend you at least relax the final > structure. One way to do that is to use AutoModel.cluster() as per > https://urldefense.com/v3/__https://salilab.org/modeller/10.5/manual/node71… > which does a basic conjugate gradients minimization. > > Ben Webb, Modeller Caretaker -- Dr Marco Sette, PhD. Department of Chemical Sciences and Technology University of Rome, "Tor Vergata" via della Ricerca Scientifica, 00133, Rome, Italy e-mail: sette(a)uniroma2.it Tel.: +39-0672594424 -- Questa email è stata esaminata alla ricerca di virus dal software antivirus Avast. www.avast.com

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D-Ala
by Xiaosa Wu 22 Oct '24

22 Oct '24

Hi all, I tried to use modeller10.4 to build a homology model for a peptide, which contains a D-Ala. Here the following steps I did: 1: in modlib/top.lib, Copy topology entry of L-Ala, then change From IC N C *CA CB 1.4592 114.4400 123.2300 111.0900 1.5461 IC N C *CA HA 1.4592 114.4400 -120.4500 106.3900 1.0840 To IC N C *CA CB 1.4592 114.4400 -123.2300 111.0900 1.5461 IC N C *CA HA 1.4592 114.4400 120.4500 106.3900 1.0840 Save as DAL 1. In modlib/top_heav.lib, I copied the topology entry for L-Ala and modified it similarly. 2. Added 'DAL' information into modlib/resty.lib. Despite following these steps, when I ran Modeller10.4, the D-Ala in the peptide appeared identical to L-Ala. Could someone please advise on what might be causing this issue? Thank you so much. Wu

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Modeller 10.6 release
by Modeller Caretaker 22 Oct '24

22 Oct '24

A new version of Modeller, 10.6, is now available for download! Please see the download page at https://salilab.org/modeller/ for more information. If you have a license key for Modeller 9 or 10, there is no need to reregister for Modeller 10.6 - the same license key will work. (It won't do any harm to reregister if you want to, though!) 10.6 is a minor update that adds support for Python 3.13, and modifies the behavior of Alignment.append_sequence() to make it easier to construct multiple-sequence alignments containing chain breaks. If you encounter bugs in Modeller 10.6, please see https://salilab.org/modeller/10.6/manual/node10.html for information on how to report them. Note: you are receiving this email either because you subscribed to the modeller_usage mailing list, or you provided this address when you requested a Modeller license and you ticked the "notify me of new releases" box. In the latter case, if you no longer wish to receive announcements of new Modeller releases, simply unsubscribe from the modeller_announce mailing list, or reply to this email and let us know. Ben Webb, Modeller Caretaker -- modeller-care(a)salilab.org https://salilab.org/modeller/ Modeller mail list: https://salilab.org/mailman/listinfo/modeller_usage

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Average the models
by Marco Sette 21 Oct '24

21 Oct '24

Dear all, I have obtained five models of a protein with Modeller and I am analyzing them in relation to the wt. There are of course small deviations, and such differences affect some physical properties. In your opinion, should I analyze the separate models or I can take the average structure? In NMR, people often use an average structure so I wonder if it makes sense in the modelling field. Thanks a lot for your help, Best, Marco -- Dr Marco Sette, PhD. Department of Chemical Sciences and Technology University of Rome, "Tor Vergata" via della Ricerca Scientifica, 00133, Rome, Italy e-mail:sette@uniroma2.it Tel.: +39-0672594424

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model different regions of a protein
by José Xavier 10 Sep '24

10 Sep '24

Dear Modeller users, I'm new here.. so sorry if this is an already answered question. I want to model a protein but the better template doesn't show ~50 aminoácids in its sequence. Is it possible to model the protein based on this template and only the region of ~50 residues based on another template? Thank you for your help Xavier

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Fwd: Error in modeller 10.5
by Victor Eduardo Rojas Pérez 04 Sep '24

04 Sep '24

---------- Forwarded message --------- De: Victor Eduardo Rojas Pérez <victor.rojas.03(a)alu.ucm.cl> Date: mar, 3 sept 2024 a las 13:11 Subject: Error in modeller 10.5 To: Modeller Caretaker <modeller-care(a)salilab.org>, < modeller_usage(a)salilab.org> Dear All, Along with greeting them cordially. I have the following error using modeller 10.5. in linux operating system. I have added the restyp RTN, retinal with % symbol in the restyp.lib file in the modlib folder but I still have this error. What else could I do to solve this error. Thank you. mod10.5 align1.py Could not find platform independent libraries <prefix> Could not find platform dependent libraries <exec_prefix> Consider setting $PYTHONHOME to <prefix>[:<exec_prefix>] 'import site' failed; use -v for traceback Traceback (most recent call last): File "align1.py", line 56, in ? a.make() # do homology modeling File "/usr/lib/modeller10.5/modlib/modeller/automodel/automodel.py", line 141, in make self.homcsr(exit_stage) File "/usr/lib/modeller10.5/modlib/modeller/automodel/automodel.py", line 611, in homcsr aln = self.read_alignment() File "/usr/lib/modeller10.5/modlib/modeller/automodel/automodel.py", line 572, in read_alignment aln.append(file=self.alnfile, align_codes=codes) File "/usr/lib/modeller10.5/modlib/modeller/alignment.py", line 82, in append allow_alternates) _modeller.ModellerError: read_al_375E> Unknown residue type,position,sequence: % 334 1 -- * Víctor E. Rojas Pérez, Msc.* *Estudiante Doctorado en Biotecnología Traslacional * * Universidad Católica del Maule * *Facultad de Ciencias Agrarias y Forestales* *e-mail: victor.rojas.03(a)alu.ucm.cl <victor.rojas.03(a)alu.ucm.cl>* -- * Víctor E. Rojas Pérez, Msc.* *Estudiante Doctorado en Biotecnología Traslacional * * Universidad Católica del Maule * *Facultad de Ciencias Agrarias y Forestales* *e-mail: victor.rojas.03(a)alu.ucm.cl <victor.rojas.03(a)alu.ucm.cl>*

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Using frcmod+off non-standard residue in modeller.
by Pedro Guillem 15 Aug '24

15 Aug '24

Hello, I'm using Modeller to mutate only. I was wondering how hard it would be to mutate any position into a non-standard residue. I have my residues in Amber format (frcmod+off), and I read that I must create the definitions in CHARMM (RST) format, so modeller understands its topology+charges,etc. I also have a PDB file and PRMTOP with the non-standard residue. How hard would it be to make this work in Modeller?. Has anybody done it before? I see that ParmED (for example) can import the Amber files and generate RST files from them, but I didn't fully understand how many files I must modify in modeller, or whether I should use the BLK option, but it is not very well documented how to do so. Thanks in advance for any info on this. Pedro

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help at second script
by Junyi.FENG＠gustaveroussy.fr 23 Jul '24

23 Jul '24

Hi, While I was running the second script which is called compare.py and is the following: from modeller import * env = Environ() aln = Alignment(env) for (pdb, chain) in (('1jfw', 'A'), ('4ogr', 'D'), ('4or5', 'C'), ('3o6l', 'C'), ('3mi9', 'C'), ('1tbc', 'A'), ('1tiv', 'A')): m = Model(env, file=pdb, model_segment=('FIRST:'+chain, 'LAST:'+chain)) aln.append_model(m, atom_files=pdb, align_codes=pdb+chain) aln.malign() aln.malign3d() aln.compare_structures() aln.id_table(matrix_file='family.mat') env.dendrogram(matrix_file='family.mat', cluster_cut=-1.0) I recieved the following message and I don't know what to do. You can find many useful example scripts in the examples\automodel directory. It is recommended that you use Python to run Modeller scripts. However, if you don't have Python installed, you can type 'mod10.5' to run them instead. C:\Program Files\Modeller10.5>cd bin C:\Program Files\Modeller10.5\bin>cd Modeller_test C:\Program Files\Modeller10.5\bin\Modeller_test>mod10.5 compare.py 'import site' failed; use -v for traceback Traceback (most recent call last): File "compare.py", line 10, in ? aln.malign3d() File "C:\Program Files\Modeller10.5\modlib\modeller\alignment.py", line 348, in malign3d edit_file_ext) _modeller.ModellerError: fit2xyz_296E> Number of equivalent positions < 3: 0 Please, help me.

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