Department of Biology
Krieger School of Arts & Sciences
B.S. 1987, St. John's University
M.S. 1991, Manhattan College
Ph.D. 1995, Johns Hopkins University
117A Mudd Hall
3400 N. Charles Street
Baltimore, MD 21218
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.
Hilser, V.J. (2013) Signalling from disordered proteins. Nature 498:308-310.
Motlagh, H.N., and V.J. Hilser. (2012) Agonism/antagonism switching in allosteric ensembles. Proc. Nat. Acad. Sci. USA 109:4134-4139.
Hilser, V.J. (2010) An ensemble view of allostery. Science 327:653-654.
Schrank, T., D.W. Bolen, 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.
Liu, T., S.T. Whitten, 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., B. Garcia-Moreno E., T.G. Oas, G. Kapp, and S.T. Whitten. (2006) A statistical thermodynamic model of the protein ensemble. Chem. Rev. 106:1545-1558.
Whitten, S.T., B. Garcia-Moreno E., 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., V.J. Hilser, 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., J.C. Lee, and V.J. Hilser. (2000) Binding sites in Escherichia coli communicate by modulating the conformational ensemble. Proc. Nat. Acad. Sci. USA. 97:12020-12025.