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The Hilser Lab - Johns Hopkins University

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117A Mudd Hall
Department of Biology
Johns Hopkins University
3400 N. Charles Street
Baltimore, MD 21218-2685


Email: hilser@jhu.edu
Office 410 516-6072
Lab 410 516-6757
Departmental fax 410 516-5213

 

Representative Publications From the Hilser Lab:


Motlagh, H.N., Wrabl J.O., Li J., and Hilser V.J. (2014) "The ensemble nature of allostery." Nature, 508(7496), 331-339. Link to paper

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.   Prot. Sci., 22: 405–417. Link to paper

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. J. Bio. Chem., 287(32), 26777-26787. Link to paper

Motlagh, H. N., and Hilser, V. J. (2012). Agonism/antagonism switching in allosteric ensembles. Proc. Nat. Acad. Sci. USA, 109(11), 4134-4139. Link to paper

Hilser, V. J., Wrabl, J. O., and Motlagh, H. N. (2012). Structural and energetic basis of allostery. Ann. Rev. Biophys., 41, 585-609. Link to paper

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. Link to paper

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. Link to paper

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. Link to paper

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. Link to paper

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. Link to paper

Hilser Lab Publications at Google Scholar and at Pub Med.

A List of All Publications From the Hilser Lab:


Motlagh, H. N., Toptygin, D., Kaiser, C. M., & Hilser, V. J. (2016). Single-Molecule Chemo-Mechanical Spectroscopy Provides Structural Identity of Folding Intermediates. Biophysical journal, 110(6), 1280-1290.

Hilser, V. J. (2016). Simultaneous Tuning of Activation and Repression in Intrinsic Disorder-Mediated Allostery. Biophysical Journal, 110(3), 2a-3a.

Anderson, J. A., Majumdar, A., & Hilser, V. J. (2016). Catching Excited States in the Act: Functional Unfolding in E. Coli Adenylate Kinase. Biophysical Journal, 110(3), 207a-208a.

Hoffmann, J., Wrabl, J. O., & Hilser, V. J. (2016). The role of negative selection in protein evolution revealed through the energetics of the native state ensemble. Proteins: Structure, Function, and Bioinformatics.

Chin, A. F., Toptygin, D., Elam, W. A., Schrank, T. P., & Hilser, V. J. (2016). Phosphorylation Increases Persistence Length and End-to-End Distance of a Segment of Tau Protein. Biophysical journal, 110(2), 362-371.

Toptygin, D., Chin, A. F., & Hilser, V. J. (2015). Effect of diffusion on resonance energy transfer rate distributions: implications for distance measurements. The Journal of Physical Chemistry B, 119(39), 12603-12622.

Hilser, V. J., Anderson, J. A., & Motlagh, H. N. (2015). Allostery vs.“allokairy”. Proceedings of the National Academy of Sciences, 112(37), 11430-11431.

Motlagh, H. N., Anderson, J. A., Li, J., & Hilser, V. J. (2015). Disordered allostery: lessons from glucocorticoid receptor. Biophysical Reviews, 7(2), 257-265.

Choi, J. H., Laurent, A. H., Hilser, V. J., & Ostermeier, M. (2015). Design of protein switches based on an ensemble model of allostery. Nature communications, 6.

Martens, A. T., Taylor, J., & Hilser, V. J. (2015). Ribosome A and P sites revealed by length analysis of ribosome profiling data. Nucleic acids research, gkv200.

Motlagh, H. N., Anderson, J. A., Li, J., & Hilser, V. J. (2015). Disordered allostery: lessons from glucocorticoid receptor. Biophysical Reviews, 7(2), 257-265.

Li, Jing, James O. Wrabl, and Vincent J. Hilser. "intrinsically Disordered Protein." Computational Approaches to Protein Dynamics: From Quantum to Coarse-Grained Methods (2014): 205.

Maillard, R. A., Liu, T., Beasley, D. W., Barrett, A. D., Hilser, V. J., & Lee, J. C. (2014). Thermodynamic Mechanism for the Evasion of Antibody Neutralization in Flaviviruses. Journal of the American Chemical Society, 136(29), 10315-10324.

Motlagh, H.N., Wrabl J.O., Li J., and Hilser V.J. (2014) "The ensemble nature of allostery." Nature, 508(7496), 331-339.

Hilser, V. J., and Whitten, S. T. (2014). Using the COREX/BEST Server to Model the Native-State Ensemble. In Protein Dynamics (pp. 255-269). Humana Press.

Hadzipasic, O., Wrabl J.O., Hilser, V.J. (2013). A Horizontal Alignment Tool for Numerical Trend Discovery in Sequence Data: Application to Protein Hydropathy. PLoS Comp. Biol. 9(10), e1003247.

Hilser V. J. (2013) Signalling from Disordered Proteins. Nature. 498, 308-310.

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.  Prot. Sci., 22: 405–417.

Hegde, M. L., Tsutakawa, S. E., Hegde, P. M., Holthauzen, L. M., Li, J., Oezguen, N., Hilser, V.J., Tainer, J.A., and Mitra, S. (2013). The Disordered C-terminal Domain of Human DNA Glycosylase NEIL1 Contributes to Its Stability via Intramolecular Interactions. J. Mol. Biol. 425, 2359-2371.

Elam, W. A., Schrank, T. P., Campagnolo, A. J., and Hilser, V. J. (2013). Temperature and Urea Have Opposing Impacts on Polyproline II Conformational Bias. Biochemistry, 2013, 52 (5), pp 949–958.

Motlagh, H.N., Li J, Thompson EB, and Hilser V.J. (2012). Interplay between allostery and intrinsic disorder in an ensemble. Biochem. Soc. Trans., 40(5), 975-80.

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. J. Biol. Chem., 287(32), 26777-26787.

Fu, Y., Kasinath, V., Moorman, V. R., Nucci, N. V., Hilser, V. J., and Wand, A. J. (2012). Coupled motion in proteins revealed by pressure perturbation.J. Am. Chem. Soc., 134(20), 8543-8550.

Motlagh, H. N., and Hilser, V. J. (2012). Agonism/antagonism switching in allosteric ensembles. Proc. Nat. Acad. Sci. USA, 109(11), 4134-4139.

Hilser, V. J., Wrabl, J. O., and Motlagh, H. N. (2012). Structural and energetic basis of allostery. Ann. Rev. Biophys., 41, 585-609.

Liu, T., Pantazatos, D., Li, S., Hamuro, Y., Hilser, V. J., and Woods Jr, V. L. (2012). Quantitative assessment of protein structural models by comparison of H/D exchange MS data with exchange behavior accurately predicted by DXCOREX. J. Am. Soc. Mass. Spectrom., 23(1), 43-56.

Hilser, V. J., and Thompson, E. B. (2011). Structural dynamics, intrinsic disorder, and allostery in nuclear receptors as transcription factors. J. Biol. Chem., 286(46), 39675-39682.

Wrabl, J. O., Gu, J., Liu, T., Schrank, T. P., Whitten, S. T., and Hilser, V. J. (2011). The role of protein conformational fluctuations in allostery, function, and evolution. Biophysical chemistry, 159(1), 129-141.

Hilser, V. J. (2011). Finding the wet spots. Nature, 469(7329), 166-167.

Schrank, T. P., Elam, W. A., Li, J., and Hilser, V. J. (2011). Strategies for the thermodynamic characterization of linked binding/local folding reactions within the native state application to the LID domain of adenylate kinase from Escherichia coli. Methods in enzymology, 492, 253.

Wrabl JO, Hilser VJ (2010) Investigating Homology between Proteins using Energetic Profiles. PLoS Computational Biol 6(3): e1000722. doi:10.1371/journal.pcbi.1000722

Hilser, V. J. (2010). An Ensemble View of Allostery. Science, 327(5966), 653-654.

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.

Vertrees, J., Wrabl, J.O., and V.J. Hilser (2009) An Energetic Representation of Protein Architecture that is Independent of Primary and Secondary Structure. Biophys. J. 97, 1461-1470.

Gu, J. and V.J. Hilser (2009) Sequence-based Analysis of Protein Energy Landscapes Reveals Non-uniform Thermal Adaptation within the Proteome. Mol. Biol. Evol. 26, 2217-2227.

Manson, A., Whitten, S.T., Ferreon, J.C., Fox, R.O. and V.J. Hilser (2009) Characterizing the Role of Ensemble Modulation in Mutation-induced Changes in Binding Affinity J. Am. Chem. Soc. 131, 6785-6793.

Gu, J. and V.J. Hilser (2009) The Significance and Impacts of Protein Disorder and Conformational Variants. In Structural Bioinformatics, Second Edition. Ed. J. Gu and P.E. Bourne, John Wiley & Sons.

Vertrees, J., Wrabl, J.O., and V.J. Hilser (2009) Energetic Profiling of Protein Folds. Meth. in Enzym., 455, 299-327.

Hilser, V.J. and S.T. Whitten (2009) Energy Flow and Allostery in an Ensemble. In Proteins: Energy, Heat and Signal Flow Eds. David M. Leitner and John E. Straub. CRC Press, Taylor & Francis Group.

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.

Wang, S., Gu, J., Larson, S.A., Whitten, S.T., and V.J. Hilser (2008) Denatured State Energy Landscapes of a Protein Structural Database Reveal the Energetic Determinants of a Framework Model for Folding. J. Mol. Biol. 381, 1184-1201.

Whitten, S.T Yang, H.-W. Fox, R.O., and V.J. Hilser (2008) Exploring the effect of conformational bias on the binding of peptides to the SEM5 C-SH3 domain. Prot. Sci. 17, 1200-1211.

Sayar K., Ugur, O., Liu, T., Hilser, V.J., Onaran, O. (2008) Exploring Allosteric Coupling in the alpha-Subunit of Heterotrimeric G Proteins Using Evolutionary and Ensemble-Based Approaches. BMC Structural Biology, 8:23.

Whitten, S.T., Garcia-Moreno E.,B., and V.J. Hilser (2008) Ligand Effects on the protein ensemble:Unifying the descriptions of ligand binding, local conformational fluctuations, and protein stability. Meth. Cell. Biol. 84, 871-891.

Whitten, S.T., Ferreon, J.C., Hamburger, J.B., and V.J. Hilser (2008) Calorimetric Determination of the Thermodynamics of Polyproline II (PII) Helix Formation in the Unfolded States of Protein. In Unfolded Proteins: From Denatured to Intrinsically Disordered Ed. Trevor Creamer, Nova Science Publishing.

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.

Whitten, S. T.; Kurtz, A. J.; Pometun, M. S.; Wand, A. J.; Hilser, V. J. (2006) Revealing the Nature of the Native State Ensemble through Cold Denaturation. Biochemistry, 2006; 45(34); 10163-101

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.

Fitch, C.A., Whitten, S.T., Hilser, V.J. and Garcia-Moreno E.,B. (2006) Molecular Mechanism of pH-driven Conformational Transitions of Proteins: Insights from Continuum Electrostatics Calculations of Acid Unfolding. Proteins, 63, 113-126.

Liu, T., Whitten, S.T., and V.J. Hilser (2006) Ensemble-based Signatures of Energy Propagation in Proteins. A New View of an Old Phenomenon. Proteins, 62, 728-738.

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.

Vertrees, J., Barritt, P., Whitten, S. and Hilser, V.J. (.2005) COREX/BEST server: a web browser-based program that calculates regional stability variations within protein structures. Bioinformatics. Aug 1;21(15):3318-9.

Ferreon, J.C., Hamburger, J. B. and V.J. Hilser (2004) An Experimental Strategy to Evaluate the Thermodynamic Stability of Highly Dynamic Binding Sites in Proteins. J. Am. Chem. Soc. 126, 12774-12775.

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. Bio. 11, 352-357.

Hamburger, J. B. Ferreon, J.C., Whitten, S.T and V.J. Hilser (2004) Thermodynamic Origins and Consequences of the Polyproline II (PII) Conformational Bias in the Denatured States of Proteins. Biochemistry. 43,9790-9799.

Ferreon, J.C. and V.J. Hilser. (2004) Thermodynamics of Binding to SH3 Domains: The Energetic Impact of Polyproline II (PII) Helix Formation. Biochemistry. 43, 7787-7797.

Larson, S.A., and V.J. Hilser. (2004) Analysis of the ‘Thermodynamic Information Content’ of a Homo sapiens Structural Database Reveals Hierarchical Thermodynamic Organization. Prot. Sci. 13, 1787-1801.

Ferguson, H.R., Fan,, X. Mukherjee, M., Luo, J., Khan, R., Ferreon, J.C., Hilser, V.J., Shope, R.E. and R.O. Fox. (2004) Directed Discovery of Bivalent Peptide Ligands to an SH3 Domain. Prot. Sci. 13, 626.

Ferreon, J.C., Volk, D.E., Luxon, B.A., Gorenstein, D.G., and V.J. Hilser.(2003) Solution Structure, Dynamics and Thermodynamics of the Native State Ensemble of the SEM5 C-terminal SH3 Domain. Biochemistry.42, 5582-5591.

Ferreon, J.C. and V.J. Hilser (2003) Ligand-induced changes in dynamics in the RT loop of the C-terminal SH3 domain of SEM-5 indicate cooperative conformational coupling. Prot. Sci. 12. 982-996.

Ferreon, J.C. and V.J. Hilser (2003) The Effect of the Polyproline II (PPII) Conformation on the Denatured State Entropy. Prot. Sci. 11, 447-457.

Wrabl, J.O., Larson, S.A., and V.J. Hilser. (2002) Thermodynamic Environments in Proteins: Fundamental Determinants of Fold Specificity. Prot. Sci. 11,1945-1957.

Wrabl, J.O., Larson, S.A., and V.J. Hilser. (2001) Thermodynamic Propensity of Amino Acids in the Native State Ensemble: Implications for Fold Recognition. Protein Sci. 10, 1032-1045 .

Whitten, S.T., Wooll, J.O., Razeghifard, R., Garcia-Moreno E.B., and V.J. Hilser. (2001) The origin of pH-dependent changes in m -values for the denaturant-induced unfolding of proteins. J. Mol. Biol 309, 1165-1175.

Hilser, V.J.. (2001) Modeling the Native State Ensemble. In Protein Structure, Stability and Folding. Methods in Molecular Biology. Ed. K. Murphy. Humana Press, Totowa, NJ, 93-115.

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.

Wooll, J.O., Wrabl, J.O. and V.J. Hilser. (2000) Ensemble Modulation as an Origin of Denaturant Independent Hydrogen Exchange in Proteins. J. Mol. Biol. 301, 247-256.

V.J. Hilser's Postdoctoral and Graduate Works:


Hilser, V.J., Dowdy, D., Oas, T., and E. Freire. (1998) Structural Distribution of Cooperative Interactions in Proteins. Analysis of the Native State Ensemble.Proc. Nat. Acad. Sci. USA. 95: 9903-9908.

Hilser, V.J., Townsend, B.D., and E. Freire. (1997) Structure-Based Statistical Thermodynamic Analysis of T4 Lysozyme Mutants: Structural Mapping of Cooperative Interactions. Biophys. Chem. 64; 69-79.

Hilser, V.J., and E. Freire. (1997) The Equilibrium Ensemble of Conformational States in Staphylococcal Nuclease. Tech. Prot. Chem., VII: 767-781.

Hilser, V.J., and E. Freire. (1997) Predicting the Equilibrium Protein Folding Pathway: Structure Based Analysis of Staphylococcal Nuclease.Proteins. 27: 171-183.

Hilser, V.J., and E. Freire. (1996) Structure Based Calculation of the Equilibrium Folding Pathway of Proteins. Correlation with Hydrogen Exchange Protection Factors. J. Mol. Biol. 262: 756-772.

Hilser, V.J., Gómez, J., and E. Freire. (1996) The Enthalpy Change in Protein Folding and Binding. Refinement of Parameters for Structure Based Calculations. Proteins 26: 123-133.

D'Aquino, A., Gómez, J., Hilser, V.J., Lee, K.H., Amzel, L.M. and E. Freire. (1996) The Magnitude of Backbone Conformational Entropy Change in Protein Folding.Proteins 25: 143 156.

Hilser, V.J., and E. Freire. (1995) Quantitative Analysis of Conformational Equilibrium Using Capillary Electrophoresis: Applications to Protein Folding.Anal. Biochem. 224: 465-485.

Gomez, J., Hilser, V.J., Xie, D., and E. Freire. (1995) The Heat Capacity of Proteins.Proteins 22: 404-412.

Rudnick, S.E., Hilser, V.J., and G.D. Worosila. (1994) Comparison of the Utility of Capillary Electrophoresis and High-Performance Liquid Chromatography in Peptide Mapping and Separation. J. Chromatogr. 672: 219-229.

Hilser, V.J., Worosila, G.D., and S.E. Rudnick. (1993) Protein and Peptide Mobility in Capillary Electrophoresis. A comparison of Existing Models and Further Analysis. J. Chromatogr. 630: 329-336.

Hilser, V.J., Worosila, G.D., and E. Freire. (1993) Analysis of Thermally Induced Folding/Unfolding Transitions Using Free Solution Capillary Electrophoresis. Anal. Biochem. 208: 125-131.