Dear BioExcel members:
I need to study single mutation effects on a protein-ligand docking. It seems I should find the conformational change due to this mutation.
I know it may an elementary question But I really needs to find a trust-able answer;
Is any software to predict “Protein Structural changes Because of Single Mutation”? what is about MODELLER? To this aim, When do we need to run MD?
whit the best.
Hello. I was involved in a similar project some months ago. We studied the mutation by running MD simulations for both wild type (no mutations) and the mutated one. Then we performed standard trajectory analysis like RMSD to investigate any potential changes.
As far as I know, Modeller is a protein homology modelling software which is about filling missing residues using other existing experimentally derived structures of the same protein or homologs. Last time I checked it is considered to be state of the art.
Modeller is indeed a protein homology modelling software and can be used to model the 3D structure of your mutant. Unfortunately, this won’t give you any clue on the effect of such mutation on the binding with the ligand. You will need to rely on molecular docking methods, such as HADDOCK, to predict the 3D structure of your complex and compare it with the WT.
Visit http://ask.bioexcel.eu/c/haddock if you have more questions
Thank you Adrin and Panos
As I am not so expert in Modeller I would like to continue this discussion.
Panos wrote “we studied the mutation by running MD simulations for both wild type (no mutations) and the mutated one.”
My question is: did you find any reasonable Protein Structural changes Because of Single(or more) Mutation beyond the Modeller predictions?
on the other word when we say “Modeller is indeed a protein homology modelling software and can be used to model the 3D structure of your mutant.” , what is the meaning of model? it is the best in put for MD simulation or it is a trust able 3D structure?
Modeller will take a protein structure as a starting point, consider as a template, and that will be most likely your wildtype protein. Then, based on the mutated sequence of the protein you will provide, it will generate a 3D structure where all mutated residues will be replaced. Side-chains of the new residues will be optimised to comply with their surrounding environment but very few conformational changes will be introduced. There will be mainly local changes and no large scale conformational changes are to be expected.
So I would only consider this output as a very good input for an MD simulation. This can maybe give you some basic insights on several local arrangments of the protein for instance but nothing more. I’d advise to always couple that with a MD or a docking for instance if you’re studying the effet of the mutation on a ligand binding.