Title: Computational Insights into Allostery, with Bioinformatics Applications

Abstract:

We have developed computational methods for studying the influence of protein interactions on protein dynamics. These methods have yielded insight into regulation of protein function through allosteric interactions, and shed light on the "induced fit" vs. "pre-existing equilibrium/conformational selectio\n" views of ligand-binding mechanisms. They can also be used to determine locations where a protein is "ticklish," i.e., where perturbations cause a large change in protein dynamics. Such locations can be used to predict native binding sites, motivating an algorithm, called dynamics perturbation analysis (DPA), for predicting protein functional sites. DPA has been validated using test sets and compares favorably to similar methods for predicting functional sites. It also has been applied to 50,000 SCOP domains; the resulting predictions recapitulate much of the known information about binding sites and catalytic sites in SCOP domains, and have been used to develop experimentally testable hypotheses concerning protein function.

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