(681g) Designing Protein Structures and Complexes with the Molecular Modeling Program Rosetta

Proteins perform an amazingly diverse set of functions in all aspects of life. Critical to the function of many proteins are the highly specific three-dimensional structures they adopt. For this reason, there is strong interest in learning how to rationally design proteins that adopt user-defined structures. Over the last 20-years there has been significant progress in the field of computational protein design as rotamer-based sequence optimization protocols have been used to accurately design protein tertiary and quaternary structure. I will summarize how the molecular modeling program Rosetta is used to design new protein structures and describe how we have used this capability to create proteins that have important applications in research and medicine. I will highlight three protein design stories: (1) the engineering of light-inducible proteins that can be used to recruit proteins to specific locations in the cell, (2) stabilizing a surface protein from the dengue virus for use a sub-unit vaccine, and (3) the de novo design of new protein structures from pieces of naturally occurring proteins.