Vincent J. Hilser, Ph.D. , Professor
Conformational Fluctuations in Function and Disease
Conformational fluctuations have emerged as an important aspect of biological function, playing a critical role in processes ranging from molecular recognition to catalysis and allosteric coupling. Our lab is interested in elucidating the structural and energetic basis of fluctuations, as well as their functional consequences, and applying this information to the development of protein design and optimization strategies and novel fold classification and genomic approaches.
Research in our lab focuses on the development and testing of structure-based models of conformational fluctuations that can capture a broad spectrum of biophysical and functional phenomena within a unified framework. Our goal is to quantitatively link fluctuations to folding and stability, allowing us to investigate the complex interplay between ligand binding, global structural transitions and fluctuations. To challenge and refine our evolving model, we employ a number of experimental systems, using titration and scanning calorimetry, NMR spectroscopy, X-ray crystallography, CD, and fluorescence spectroscopy to provide both global and sight resolved characterizations of proteins.
Selected Publications
Gu, J. and V.J. Hilser (2008) Predicting the Energetics of Conformational Fluctuations in Proteins from Sequence: A Strategy for Profiling the Proteome. Structure, 16, 1627-1637.
Hilser, V. J. and E. B. Thompson (2007) Intrinsic Disorder as a Mechanism to Optimize Allosteric Coupling in Proteins. Proc. Nat. Acad. Sci. USA. 104, 8311-8315.
Liu, T., Whitten, S.T., and V.J. Hilser (2007) Functional Residues Serve a Dominant Role in Mediating Cooperativity of the Protein Ensemble Proc. Nat. Acad. Sci. USA. 104, 4347-4352
Hilser, V.J. , Garcia-Moreno E.,B., Oas, T.G, Kapp, G. and S.T. Whitten. (2006) A Statistical Thermodynamic Model of the Protein Ensemble. Chem. Rev. 106, 1545-1558.
Whitten, S.T., Garcia-Moreno E.,B., and V.J. Hilser (2005) Local Fluctuations Can Modulate the Coupling Between Proton Binding and Global Structural Transitions in Proteins. Proc. Nat. Acad. Sci. USA. 102, 4282-4287.
Babu, C.R., Hilser, V.J. and A. J. Wand (2004) Direct Access to the Cooperative Substructures of Proteins and the Protein Ensemble via Cold Denaturation. Nat. Struct. Mol. Biol. 11,352-357.
Pan, H., Lee, J.C. and V.J. Hilser. (2000) Binding Sites in Escherichia Coli Communicate by Modulating the Conformational Ensemble. Proc. Nat. Acad. Sci. USA. 97, 12020-12025.
