Baker, David

The goal of current research in our laboratory is to develop an improved model of intra and intermolecular interactions and to apply this improved model to the prediction and design of macromolecular structures and interactions. Prediction and design applications can be of great biological interest in their own right, and also provide very stringent and objective tests which drive the improvement of the model and increases in fundamental understanding.

The protein and design calculations are carried out using a computer program called Rosetta. At the core of Rosetta are the physical model of macromolecular interactions and algorithms for finding the lowest energy structure for an amino acid sequence (protein structure prediction) or a protein-protein complex and for finding the lowest energy amino acid sequence for a protein or protein-protein complex (protein design). Both the physical model and the search algorithms are continually being improved based on feedback from the prediction and design tests. There are considerable advantages in developing one computer program to treat these quite diverse problems: first, the different applications provide very complementary tests of the underlying physical model (the fundamental physical chemistry is of course the same in all cases), and second, many problems of current interest, such as flexible backbone protein design and protein-protein docking with backbone flexibility involve a combination of the different optimization methods.