modeller_usage November 2019

modeller_usage@salilab.org

3 participants
2 discussions

selection.mutate then optimize Vs. homology modeling for point mutations
by Ammar, Ammar (Stud. SCI) 18 Nov '19

18 Nov '19

Dear all, I hope you can give me your opinion in my case. I have a 3D structure of a wildtype protein (X-Ray) and I want to mutate one amino acid (substitution) and obtain the new structure that contains the introduced structural changes by the mutation. Also, the sequence of the protein is known. I see an example on Modeller website for a Mutated model: https://salilab.org/modeller/wiki/Mutate%20model which show how to introduce a mutation and then the conformation of the mutant sidechain is optimized by conjugate gradient and refined using some MD. Another way of doing it is to provide the PDB file and an alignment of the protein sequence and its mutant version and perform homology modelling using Modeller. Any idea which method is preferable considering that both can be performed using Modeller to achieve the same goal here? Thank. Best regards.

2 1

Modelling in/dels and residue substitutions
by Jared Slosberg 12 Nov '19

12 Nov '19

Hello, I am interested in creating models for variants of a protein with a known cryo-EM structure. My approach for the substitutions is to use the mutate_model script. However, I would also like to model predicted changes in structure to nearby residues. I altered the script in this way in an attempt to optimize over a range of residues, but I saw no difference in the resulting model than with only the one residue selected. modelname, respos, restyp, chain, start, stop, = sys.argv[1:] ... s = selection(mdl1.chains[chain].residues[start],mdl1.chains[chain].residues[stop]) Could you tell me if this change to the script would be expected to alter the resulting model, or if there is a better approach? As well, my approach to modelling deletions is to create a manual alignment in which the residues around the deletion are unaligned from the template, so that they fold freely, and choosing the model [ generated with model_single.py ] with the lowest DOPE score if inspection looks good. [Here, GFF deleted]. one segment of query: FNSSAFFFSVV---------FL aligned segment of template: FNSSA------FFFSGFFVVFL However, this has obviously left the ends of the aligned sections fixed in space, so that the region that I want to fold "freely" is fixed at these two points. This results in them "stretching out" rather than being able to fold as I would like. I hope that I am being clear. Is there better method to create variants with insertions that is more flexible? Thank you for your time, Jared

2 1

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modeller_usage November 2019