Hello,

I don't think any online tool can be used to understand the changes in structure/function due to substitutions. Effects on structure may be studied using modeling and simulation studies. But, it is up to you to decipher what these structural changes mean in the context of your protein.

But, what I would suggest is to first start out with the structure of the protein or the reference protein, if available. Now with the structure in hand, you can map out the substituted residues and their positions in the structure (in a pocket or surface or protein core). Say if your protein is an enzyme, then a residue substitution in the active-site pocket may significantly alter the substrate binding, kinetics. Similarly, if the substitutions are on protein surfaces, it may affect the binding affinity of the protein to its partners or even the specificity of the partners. In this case however, one should consider the possibility of co-evolving positions on both partner proteins, that do not affect the function much. So, the next step would be to also look for possible partners and study their protein sequences and structure, from literature or protein-interaction network databases. I am not sure if such as database is available for viral proteins. For viral proteins, you may need to consider possible partners in the host too.

A lot of information can be derived from the structure in this regard, but it requires some domain knowledge about the protein. Also, these would just be rational predictions, that eventually need to be tested experimentally to see if they hold ground.

Niccoló Alfano

These are the tools used to predict the effects of variants.

https://sift.bii.a-star.edu.sg/

http://provean.jcvi.org/index.php

http://www.mutationtaster.org/

http://mutpred.mutdb.org/

http://mutationassessor.org/r3/

Hope it may help you.

Hi guys, thank you both for your feedbacks! very helpful. Cheers