Comparing Protein-Protein Docking interactions between WT and mutant proteins

[Anonymous]

Hello,

I am new to the ROSIE server and Rosetta. I have found it very useful so far but am still learning.  What I would like to use the server for is to design mutant variants of one protein that will provide selectivity for one binding partner over another.  I have done the sequence tolerance task and I think I understand the results but now I would like to build in some predicted residues and see how they effect binding to the desired binding partner and an off-target binding partner.  Can this be done on the ROSIE server?  My main concern is if I dock wt-protein-A to it’s receptor protein B and off-target protein C. Can I reliably compare the docking energies of these two experiments? Then is I make a mutant of Protein-A and do the same can I again reliably rank the best mutations based on the dockign energies?

 

Thanks!

[Anonymous]

This sort of mutational prediction isn’t really covered by the ROSIE server at the moment. See the Sequence Tolerance applicaiton (http://rosie.rosettacommons.org/documentation/sequence_tolerance) for something that might be close — it will identify mutations which are tolerated by the two different partners (from two different runs), from which you may be able to tease out mutations which are tolerated in one but not the other. From this you can get suggestions as to selectivity.

If you want to do anything more complex, you’re likely going to need to do it with Rosetta run on a local machine. See https://www.rosettacommons.org/software for information on how to obtain Rosetta, and then see https://www.rosettacommons.org/demos/latest/Home for tutorials on how to use Rosetta. (These are also availible in the Rosetta download directory, in the Rosetta/demos/tutorials/ directory) If you have further questions, you can always ask them in the Rosetta section of the forum here.

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