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The Hilser Lab - Johns Hopkins University

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117A Mudd Hall
Department of Biology
Johns Hopkins University
3400 N. Charles Street
Baltimore, MD 21218-2685

Office 410-516-6072
Lab 410-516-6757
Departmental fax 410-516-5213

We are interested in elucidating the physical and energetic basis as well as the functional consequences of conformational heterogeneity in proteins, and applying this information to the development of novel fold classification schemes and protein design strategies.

It is well established, primarily from NMR spectroscopy, that folded proteins undergo local conformational fluctuations that involve transient excursions from the canonical structure. Because of these fluctuations, the native states of proteins are actually ensembles composed of many similar, interconverting conformational microstates. Despite knowledge of their existence, however, the probability and structural character of the microstates sampled by proteins are not well understood, nor is the manner in which these fluctuations are coupled to important functional processes such as catalysis, allostery, and signal transduction.

Research in our lab is focused on the experimental characterization of conformational fluctuations, the development and refinement of a general ensemble-based model for fluctuations, and the projection of this thermodynamic model into genomic analysis. Our goals are to unify the description of protein behaviors in such a way as to understand their relationships at the phenomenological level, to codify these relationships in a simple structure-based model, and to apply our model to a number of experimental systems that can be used to test and refine our approach.