I have an enzyme and I want to optimize its sequence to increase its binding to one protein and decrease its binding to another protein at the same time. I recently attended Rosetta workshop and learn about multi state protein design which can be used to increase affinity of an antibody to its ensemble of antigen, but I am not sure whethe it is applicable to my case. I would appreciate any suggestions.
Rosetta has at least two multistate design tools.
mpi_msd (https://www.rosettacommons.org/docs/latest/application_documentation/design/mpi-msd) (https://www.rosettacommons.org/demos/latest/protocol_capture/multistate_apl/README) will definitely work for this purpose. You can set up explicitly negative states for the decreased binding desired.
RECON probably will as well.
RECON currently does not handle negative design. It will only work with systems where you're attempting to improve the energy of all states.