Hi, there hope everyone is fine. I am designing a research proposal and I came across a situation that the protein on which I want to work is actually a complex of 6 different proteins working collaboratively from which 3 proteins are found in PDB database with co-crystalized structures remaining three are not present.
My query is that can I go for homology modelling of the remaining 3 proteins and then interact them with each other to construct a complete complex of proteins. is it possible because their functions are known and validated by wet lab experimentations but the complete complex is not known that how these all proteins interact with each other and in which conformations?
I was thinking that I can go for homology modelling and then search for a conformational search that interacts with other proteins with a high affinity is it a feasible approach and what could be the possible limitations.
Looking forward to your responses your inputs will be appreciated.
Thanks
Did you search the pdb with the sequence of the proteins (https://www.rcsb.org/search/advanced)? If you can find homologs of the proteins you could not find directly, homology modelling should be no problem, e.g using SwissModel (https://swissmodel.expasy.org)
Hi,
I agree with Annemarie Honegger answer, first, try to perform a deep search for your sequences in the PDB database and if you could not find structures try to model them using SwissModel, I-TASSER, or Phyre2 webservers. If you would like to model your sequences manually go for Modeler (https://salilab.org/modeller/).
Cheers..!!
Recently, the protein structure prediction programs AlphaFold and RosettaFold have been applied to the problem of predicting the structure of protein complexes as well as the structure of individual polypeptides. Perhaps you could consider using these programs to predict the structure of your proteins and then the complex.
I agree with Shapiro on the use of Alphafold. It’s a great tool for this. I would also use Molecular Dynamic simulations to study these interactions.
Best of luck!
Thank you for all these useful insights I will definitely go through it. Actually the problem is that I am working on a complex of proteins there are 6 different proteins making complex in PDB the complex of only 4 proteins are available but additional 2 proteins are not in the complex I want to make a complete complex of 6 proteins than wanna move to MD simulations for objective oriented tasks. That's why I was confused either I can go with homology modeling or there should be any other better way to do this.
You would first predict each of the proteins separately, as most of the modelling programs will not be able to treat multi-chain structures in one go. Then, you can assemble the complex, using available structures as templates to model the interaction wherever possible, and use docking for those components for which no suitable templates can be found. Be careful with models from alpha fold - the way it includes unfolded regions in the model may lead to clashes when you try to assemble the complex. It may be better to omit those low-confidence regions and only model them in once you have assembled the complex.
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