Professor and Chair
Vincent Hilser is a professor and chair of the Department of Biology. He received his PhD from Johns Hopkins University and his research focuses on conformational fluctuations and intrinsic disorder in allosteric signaling, disease, and evolution.
Conformational Fluctuations and Intrinsic Disorder in Allosteric Signaling, Disease and Evolution
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.
Please visit the Hilser Lab Website for more information.
Motlagh, H.N., Wrabl J.O., Li J., and Hilser V.J. (2014). The ensemble nature of allostery. Nature, 508 (7496), 331-339.
Elam, W.A.., Schrank, T. P., Campagnolo, A. J., and Hilser, V. J. (2013). Evolutionary conservation of the polyproline II conformation surrounding intrinsically disordered phosphorylation sites. Protein Science, 22: 405–417.
Li, J., Motlagh, H. N., Chakuroff, C., Thompson, E. B., and Hilser, V. J. (2012). Thermodynamic dissection of the intrinsically disordered N-terminal domain of human glucocorticoid receptor. Journal of Biological Chemistry, 287(32), 26777-26787.
Motlagh, H. N., and Hilser, V. J. (2012). Agonism/antagonism switching in allosteric ensembles. Proceedings of the National Academy of Sciences,109(11), 4134-4139.
Hilser, V. J., Wrabl, J. O., and Motlagh, H. N. (2012). Structural and energetic basis of allostery. Annual review of biophysics, 41, 585-609.
Schrank, T., Bolen, D.W., and V.J. Hilser (2009). Rational Modulation of Conformational Fluctuations in Adenylate Kinase Reveal a Local Unfolding Mechanism for Allostery and Functional Adaptation in Proteins. Proc. Nat. Acad. Sci. USA. 106, 16984-16989.
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.
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.
Pan, H., Lee, J.C. and V.J. Hilser (2000). Binding Sites in Escherichia Coli Dihydrofolate Reductase Communicate by Modulating the Conformational Ensemble. Proc. Nat. Acad. Sci. USA 97, 12020-12025.
Associate Research Scientist
James Otto Wrabl