Rosetta Design

Advances in experimental protein structure determination methods (X-ray crystallography, NMR and EPR spectroscopy, and cryo-electron microscopy (cryo-EM)) have begun to allow for predictions of protein stability and function. These experimentally derived biophysical measures can be used in computational frameworks to engineer proteins for intended purposes including increased stability, novel function, and improved ligand-binding. The purpose of protein design is to find potential amino acid sequences that can maintain at least one previously determined or predicted, stable 3D protein structure. Within Rosetta, there are many protocol options for protein design. For example, single-state design in Rosetta focuses on optimizing the binding affinity of a single ligand to the protein of interest. This method targets design within the protein-ligand interface. Protein design can also proceed by multistate design where the binding affinities of the protein for multiple interacting partners is considered. More information about protein design protocols in Rosetta and relevant tutorials can be found at the RosettaCommons:

Relevant Bibliography:
[1]Schoeder, C.T., Schmitz, S., Adolf-Bryfogle, J., Sevy, A.M., Finn, J.A., Sauer, M.F., Bozhanova, N.G., Mueller, B.K., Sangha, A.K., Bonet, J., Sheehan, J.H., Kuenze, G., Marlow, B., Smith, S.T., Woods, H., Bender, B.J., Martina, C.E., del Alamo, D., Kodali, P., Gulsevin, A., Schief, W.R., Correia, B.E., Crowe, J.E., Meiler, J., Moretti, R. Modeling Immunity with Rosetta: Methods for Antibody and Antigen Design. Biochemistry. 11, 825-846. (2021)
[2]Bozhanova, N.G., Harp, J.M., Bender, B.J., Gavrikov, A.S., Gorbachev, D.A., Baranov, M.S., Mercado, C.B., Zhang, X., Lukyanov, K.A., Mishin, A.S., Meiler, J. Computational redesign of a fluorogen activating protein with Rosetta. PLoS Computational Biology. 17, 11. (2021)