Colloquium Details

Computer-based Design of Protein-Protein Interactions

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

Synopsis:

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.

Notes:

In-person attendance only available to those with active NYU ID cards. All individuals must show the Daily Screener green pass in order to gain entry to the building.


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