Systems Biology Group Meeting

Presenter: James Eastwood, Ph.D. Candidate, New York University

Title: Static and Dynamic Views of Peptoid Macrocycles in Theory and Experiment

Abstract: Cyclic oligomers of N-substituted glycine hold promise as next-generation therapeutics that can target “undruggable” protein-protein interactions. These “peptoid” macrocycles are substantially more rigid than their linear counterparts, but a growing body of literature is identifying their conformational flexibility as an essential factor in their activity. Our theoretical studies of peptoid macrocycles have predicted a single correlated motion, which we call the “snap move,” that can describe transitions between the preponderance of theoretical conformations. New experimental data provides further evidence for the importance of the snap move and illustrates some of its structural implications. We have used the conformations identified in these theoretical studies as the starting points for Rosetta design of peptoid macrocycles targeting protein surfaces.