I am currently studying the effect of one of the mutation in the receptor protein. One of the mutation involves substitution of one AA and also addition of 2 AAs (KTVN -> KTVKEA). Would there be any way to predict change in structure or function (since the mutation is in the kinase domain)? Since I am not familiar with structural studies, it is difficult to find a way of doing it. Many Thanks in advance
You can try using the following web servers:
SIFT : a web server for predicting effects of amino acid substitutions on proteins.
PoPMuSiC 2.1: a web server for the estimation of protein stability changes upon mutation and sequence optimality.
Dear Jee Hwan Ahn ,
Indeed, as suggested by Tushar Chakraborty SIFT might be relevant for your research question. See for more info: Sim, N. L., Kumar, P., Hu, J., Henikoff, S., Schneider, G., & Ng, P. C. (2012). SIFT web server: predicting effects of amino acid substitutions on proteins. Nucleic acids research, 40(W1), W452-W457.
Obviously, there are nowadays numerous programs related to structure prediction, two nice suggestions might be:
Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N., & Sternberg, M. J. (2015). The Phyre2 web portal for protein modeling, prediction and analysis. Nature protocols, 10(6), 845-858.
Roy, A., Kucukural, A., & Zhang, Y. (2010). I-TASSER: a unified platform for automated protein structure and function prediction. Nature protocols, 5(4), 725-738.
In general, it is important to realize that single (or close to single) point mutations most of the time will not change a 3-D structure of a protein. If you are ‘lucky’ it might change the secondary structure. You could consider one (or custom is to use at least two) secondary structure prediction programs available. Like SOPMA, PsiPred etc.
There are ligand-protein and protein-protein prediction programs were other might have some good suggestions for you. Hope this answer helps you somewhat.
Best regards.
Also check https://www.nature.com/articles/s41598-018-22531-2
Whatever structure you will model after your mutations, remember that the structure of proteins depends on water. In silico models are inadequate even if you minimize them. A reliable final structure is got only with molecular dynamics in the presence of water. If the dynamics go to equilibrium, the model is stable and therefore approaches reality in solution.
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