Protein-Protein Interaction After Mutation

Question

[Jean-Paul Abbuehl]

Hi everyone,

I have a simple request: lets say we have 4 proteins. I know from several databases (Stitch, Uniprot, Etc..) that protein A binds directly to 3 different proteins (B, C, D), with experimental evidences.

If protein A has point mutation(s) or INDEL at known position(s), is there a way to predict its impact (Yes/No) on interaction with the other proteins. I am not interested in the function itself, but just the interaction (and maybe the stability of protein A)

Eg. In protein A, G aa replaced by Y aa at position 235 -> protein A cannot bind anymore to protein B, but can still bind proteins C and D.

Ideally I need to implement that locally because I have several proteins to test... (up to 100)

I have the feeling this is a trivial request that should have been already addressed, but I cannot find any hints in the web.

Could you give me some recommendations/papers/links/database where I could start first (instead of reinventing the wheel ahah)

Thank you very much

Best

Jean-Paul

[Tommy Carstensen]

@Jean-Paul What method did you end up using? Thanks.

Answer 1

[AsoInfo]

Firstly perform the macro-molecular docking between the wild-type protein and their corresponding ligands then perform the same process using the mutated protein instead of normal protein. This will help you in judging whether the mutation had effected the binding sites or not.

There are several softwares for docking like Hex, PyMOL (plug-in of autdock), AutoDock (it also gives you the interaction). You will find numerous papers related to macro-molecular docking on the website. There are many online servers also which can help you in this regard like ZDock, RosettaDock. There are also many linux based softwares also which will make your tasks feasible.

[Jean-Paul Abbuehl]

Amazing I'll see what I can do in that direction Thank you

Answer 2

[Michael Kuhn]

No solution, but a paper on this concept: Edgetic perturbation models of human inherited disorders

Answer 3

[Hayssam]

Hi,

I found the study of Wang et al. 2011, Three-dimensional reconstruction of protein networks provides insight into human genetic disease quite interesting and scientifically sound. Might be relevant for you too.