Speaker: Brian Kuhlman, Assistant Professor of Biochemistry and Biophysics, University of North Carolina, Chapel Hill
Location: Warren Weaver Hall 1302
Date: February 6, 2009, 11:30 a.m.
Host: Rich Bonneau
Strategies have been developed for three problems in protein interface design: 1) increasing the affinity of naturally occurring interactions, 2) redesigning protein-protein binding specificities, and 3) designing interactions from scratch. All three approaches make use of the sequence and backbone optimization protocols in the molecular modeling program Rosetta. In general, designs that make use of hydrophobic interactions have been more successful than designs that rely on novel hydrogen bonding networks. This is not ideal as incorporating hydrophobic residues on to the surface of proteins can result in non-specific binding and aggregation. To design more polar interfaces we are exploring a strategy that combines molecular modeling with combinatorial screening. Independent sequence optimization trajectories are performed on a large set of perturbed interfaces, and then used to generate amino acid profiles for each residue at the interface. Libraries based on these profiles are screened for binding. This strategy has been used in one case to design a hydrogen bonding network around a novel histidine residue placed at the center of an interface.
Refreshments will be offered starting 15 minutes prior to the scheduled start of the talk.