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Facile Determination of Protein Dynamics and Structure with Enhanced Amide Hydrogen Deuterium Exchange Mass Spectrometry (DXMS)

presented by

Virgil L. Woods Jr.
University of California, San Diego

April 08, 2004

The Scripps Research Institute, W.M. Keck Foundation Amphitheater


Background:

Dr. Woods is Associate Professor of Medicine, at the University of California, San Diego. In 1989, with the guidance of Walter Englander, he began working on the development and refinement of peptide hydrogen exchange methodologies into robust tools for the high speed, high resolution characterization of protein structure and function. Automation of the refined methods of data acquisition and computational data reduction were completed two years ago and the resulting high- throughput/ high- resolution peptide amide hydrogen/ deuterium exchange- mass spectrometry technology (termed "DXMS") was then made available to collaborators at UCSD and elsewhere. Dr. Woods is the founding scientist of a biotech startup (ExSAR, Inc) that is dedicated to the commercial exploitation of hydrogen exchange technology.

Collaborative studies performed over the past two years have demonstrated the power of DXMS to rapidly and precisely define protein domain organization, follow the changes in regional stability of proteins before and after they are bound to protein or nucleotide binding partners, probe the binding of cAPK regulatory subunits to the cAPK catalytic subunit or to cyclic nucleotides, and localize and measure free energy transmission through hemoglobin while undergoing conformational change. Additional collaborations led to the development of algorithms and software presently employed for deconvolution of aggregate peptide fragment exchange data into amide specific exchange rate determinations.

Abstract:

Dr. Woods? presentation will focus on collaborative studies performed with the Joint Center for Structural Genomics that have demonstrated the ability of DXMS- derived insights into the presence of disordered regions in proteins to guide the design of well- crystallizing protein constructs. He will also discuss what is perhaps the most ambitious application of this technology to date, which aims to develop high throughput methods for determining protein 3-D structures employing DXMS data to constrain ab-initio structural prediction.

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