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.

Wrabl, J.O., Beale, J., Fortunato, G., van den Berg Monsalve, A. and V.J. Hilser (2026) Ensemble Molecular Mimicry correlates with antibody cross-reactivities in proteome-wide studies.  Front. Immunol.  17:1749369.

Voortman-Sheetz, K. Wrabl, J.O. and V.J. Hilser (2025) Impact of local unfolding on the evolution of regional sequence preferences in proteins. Prot. Sci. 34(3) e70015.

Hilser, V.J., Wrabl, J.O., Millard, C.E.F., Andrick, A., Brantley, S., Pearce, M., Rehfus, J., Russo, M., Voortman-Sheetz, K. (2025) Statistical Thermodynamics of the Protein Ensemble in Mediating Function and Evolution. Ann. Rev. Biophys. 54, 227-247.  

Chin, A.F., Wrabl, J.O. and V.J. Hilser (2022) A thermodynamic atlas of proteomes reveals energetic innovation across the tree of life. Mol. Biol. Evol. 39, 1-13.

Cho, M-H., Wrabl, J.O., Taylor, J.T. and V. J. Hilser (2020) Hidden Dynamic signatures drive substrate selectivity in the disordered phosphoproteome. Proc. Nat. Acad. Sci. USA. 117, 23606-23616.

Saavedra^, H.G., Wrabl, J.O., Anderson^, J.A., Li, J. and V. J. Hilser (2018) Dynamic allostery can drive cold adaptation in enzymes. Nature. 558, 324-328.

Li, J., White, J.T, Saavedra, H., Wrabl, J.O., Motlagh, H.N., Liu, K., Sowers, J., Schroer, T.A., Thompson, E.B., and V.J. Hilser (2017) Genetically tunable frustration controls allostery in an intrinsically disordered transcription factor. eLife. 6 e30688.

Hilser, V.J., Anderson, J.A., and H.N. Motlagh (2015) Allostery vs. “allokairy”. Proc. Nat. Acad. Sci. USA.  112, 11430-31. 

Motlagh, H.N., Wrabl, J.O., Li, J and V.J. Hilser (2014) The Ensemble Nature of Allostery. Nature.  508, 331-339.

Motlagh, H.N., and V.J. Hilser (2012) Agonism/Antagonism Switching in Allosteric Ensembles. Proc. Nat. Acad. Sci. USA.  109, 4134-39. PMID: 22388747; PMCID: PMC3306695.

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, 16984-189.

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, 8311-15.

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, 4347-52.

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, 4282-87.

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, 12020-25.