Office: CENT 408B
Phone: (512) 245-7893
Fax: (512) 245-2374email: firstname.lastname@example.org
Honors and Awards
Areas of Interest
Protein thermodynamics, biophysics, computational chemistry
The Whitten group investigates the thermodynamic stability of protein macromolecules to develop molecular descriptions of biological activity. Briefly, we combine experimental and computational techniques to characterize how protein macromolecules fold, interact with ligands, respond to pertubations (i.e., mutation, temperature and pH changes) and perform biological tasks. Our experiments typically use equilibrium thermodynamics to measure interaction and folding energies, whereas computer simulations are used to develop molecular models that describe the measured energetics. Currently, three projects are active in my group:
Project 1: Structural characterization of intrinsically disordered proteins (IDPs). IDPs are biologically common, yet little is known about their structural properties and, consequently, the physical basis of their biological activities.
Project 2: Development of room-temperature methods to investigate protein cold denaturation and characterize protein structures.
Project 3: Molecular interactions that control the self-assembly of protein into nanofibril structures, as a model for certain neurodegenerative disorders.
Hilser, V. J.; Whitten, S. T.* Using the COREX/BEST Server to model the native state ensemble. Methods Mol. Biol. 2014, 1084, 255-269.
Langridge, T. D.; Tarver, M. J.; Whitten, S. T.* Temperature effects on the hydrodynamic radius of the intrinsically disordered N-terminal region of the p53 protein. Proteins 2013, doi: 10.1002/prot.24449.
Schaub, L. J.; Campbell, J. C. ; Whitten, S. T.* Thermal unfolding of the N-terminal region of p53 monitored by circular dichroism spectroscopy. Protein Sci. 2012, 21, 1682-1688.
Campbell, J. C.; Whitten, S. T.* Mutational analysis of m-values as a strategy to identify cold-resistant substructures of the protein ensemble. Proteins 2012, 80, 184-193.
Wrabl, J. O.; Gu, J.; Liu, T.; Schrank, T. P.; Whitten, S. T.; Hilser, V. J.* The role of protein conformational fluctuations in allostery, function, and evolution. Biophys. Chem. 2011, 159, 129-141.
Bell-Upp, P.; Robinson, A. C.; Whitten, S. T.; Wheeler, E. L.; Lin, J.; Stites, W. E.; García-Moreno E., B.* Thermodynamic principles for the engineering of pH-driven conformational switches and acid insensitive proteins. Biophys. Chem. 2011, 159, 217-226.
Hilser, V. J.; Whitten, S. T. Energy flow and allostery in an ensemble. In Proteins: Energy, Heat, and Signal Flow; CRC Press, 2010; pp 341-360.
Manson, A. C.; Whitten, S. T.; Ferreon, J. C.; Fox, R. O.; Hilser, V. J.* Characterizing the role of ensemble modulation in mutation-induced changes in binding affinity. J. Am. Chem. Soc. 2009, 131, 6785-6793.
Wang, S.; Gu, J.; Larson, S. A.; Whitten, S. T.; Hilser, V. J.* Denatured-state energy landscapes of a protein structural database reveal the energetic determinants of a framework model for folding. J. Mol. Biol. 2008, 381, 1184-1201.
Whitten, S. T.; Yang, H. W.; Fox, R. O.; Hilser, V. J.* Exploring the impact of conformational bias on the binding of peptides to the SEM-5 SH3 domain. Protein Sci. 2008, 17, 1200-1211.
Whitten, S. T.; García-Moreno E., B.; Hilser, V. J.* Ligand effects on the protein ensemble: unifying the descriptions of ligand binding, local conformational fluctuations, and protein stability. Methods Cell Biol. 2008, 84, 871-891.
Whitten, S. T.; Ferreon, J. C.; Hamburger, J. B.; Hilser, V. J. Calorimetric determination of the thermodynamics of polyproline II (PII) helix formation in the unfolded states of protein. In Unfolded proteins: from denatured states to intrinsically disordered; Nova Science Publishers, Inc, 2008; pp 169-193.
Liu, T.; Whitten, S. T.; Hilser, V. J.* Functional residues serve a dominant role in mediating the cooperativity of the protein ensemble. Proc. Natl. Acad. Sci. USA 2007, 104, 4347-4352.
Whitten, S. T.; Kurtz, A. J.; Pometun, M. S.; Wand, J. A.; Hilser, V. J.* Revealing the nature of the native state ensemble through cold denaturation. Biochemistry 2006, 45, 10163-10174.
Fitch, C. A.; Whitten, S. T.; Hilser, V. J.; García-Moreno E., B.* Molecular mechanisms of pH-driven conformational transitions of proteins: Insights from continuum electrostatics calculations of acid unfolding. Proteins 2006, 63, 113-126.
Liu, T.; Whitten, S. T.; Hilser, V. J.* Ensemble-based signatures of energy propagation in proteins: a new view of an old phenomenon. Proteins 2006, 62, 728-738.
Hilser, V. J.*; García-Moreno E., B.; Oas, T. G.; Kapp, G.; Whitten, S. T. A statistical thermodynamic model of the protein ensemble. Chem. Rev. 2006, 106, 1545-1558.
Whitten, S. T.; García-Moreno E., B.; Hilser, V. J.* Local conformational fluctuations can modulate the coupling between proton binding and global structural transitions in proteins. Proc. Natl. Acad. Sci. USA 2005, 102, 4282-4287.
Vertrees, J.; Barritt, P.; Whitten, S. T.; Hilser, V. J.* COREX/BEST server: a web browser-based program that calculates regional stability variations within protein structures. Bioinform. 2005, 21, 3318-3319.
Olmsted, S. S.; Khanna, K. V.; Ng, E. M.; Whitten, S. T.; Johnson, O. N. III; Markham, R. B.; Cone, R. A.; Moench, T. R.* Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model. BMC Infect. Dis. 2005, 5, 79-87.
Hamburger, J. B.; Ferreon, J. C.; Whitten, S. T.; Hilser, V. J.* Thermodynamic mechanisms and consequences of the polyproline II (PII) structural bias in the denatured states of proteins. Biochemistry 2004, 43, 9790-9799.
Whitten, S. T.; Wooll, J. O.; Razeghifard, R.; García-Moreno E., B.; Hilser, V. J.* The origin of pH-dependent changes in m-values for the denaturant-induced unfolding of proteins. J. Mol. Biol. 2001, 309, 1165-1175.
Whitten, S. T.; García-Moreno E., B.* pH dependence of stability of staphylococcal nuclease: evidence of substantial electrostatic interactions in the denatured state. Biochemistry 2000, 39, 14292-14304.