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Dr. Steve Whitten - Associate Professor

Dr. Steve Whitten

Contact Information

Office:  CENT 408B

Phone:  (512) 245-7893

Fax:  (512) 245-2374


Educational Background

  • B.S., Physics, University of Nebraska at Omaha (Omaha, NE) 1994
  • Ph.D., Biophysics, The Johns Hopkins University (Baltimore, MD) 2000
  • Postdoctoral Fellow, National High Magnetic Field Laboratory and Florida State University (Tallahassee, FL) 2000
  • Postdoctoral Fellow, University of Texas Medical Branch (Galveston, TX) 2001-2006

Honors and Awards

  • Invited speaker, 252nd ACS National Meeting, August 2016
  • Invited speaker, 71st Calorimetry Conference, August 2016
  • Award R15GM115603 from the National Institute of General Medical Sciences of the National Institutes of Health, August 2015
  • Invited seminar, Texas Woman's University, Dept of Chemistry and Biochemistry, January 2015
  • Co-organizer, 2014 Gibbs Conference on Biothermodynamics
  • Invited speaker, 69th Calorimetry Conference, July 2014
  • Invited talk, Committee on Academic and Workforce Success of Texas Higher Education Coordinating Board, June 2014
  • Invited seminar, University of Kansas Medical Center, Dept of Biochemistry and Molecular Biology, March 2014
  • Invited speaker, 5th Texas Enzymes Mechanisms Conference, January 2014
  • Texas State University, Research Enhancement Program Award - 2013
  • Invited speaker, Triangle MRSEC Seminar Series, October 2013
  • Invited speaker, 27th Gibbs Conference on Biothermodynamics, October 2013
  • Texas Higher Education Coordinating Board Advanced Research Program Award - 2011
  • Texas State University, Research Enhancement Program Award - 2011
  • Invited speaker, Southwest Regional Meeting of the ACS, November 2011
  • Research Corporation for Science Advancement, Cottrell College Single Investigator Award - 2010
  • Invited seminar, Baylor University, Dept of Chemistry and Biochemistry, November 2010
  • Invited seminar, University of Nebraska at Omaha, Dept of Physics, March 2010
  • Texas State University, Research Enhancement Program Award - 2009
  • Invited seminar, University of Iowa, Dept of Biochemistry, April 2009
  • Invited seminar, University of Nebraska Medical Center, Dept of Pharmaceutical Sciences, January 2009
  • Invited seminar, Tulane University Health Sciences Center, Dept of Biochemistry, December 2008
  • Invited speaker, 16th Annual Texas Protein Folders Meeting, March 2008
  • Invited seminar, University of Colorado at Denver Health Sciences Center, Dept of Pharmaceutical Sciences, November 2007
  • Invited speaker, 20th Gibbs Conference on Biothermodynamics, October 2006
  • American Heart Association Postdoctoral Fellowship - 2000

Areas of Interest

Protein thermodynamics, biophysics, computational chemistry


Research in the Whitten Group

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.


Whitten Figure


Recent Publications

English, L. R.; Tilton, E. C.; Ricard, B. J.; Whitten, S. T.* Intrinsic α helix propensities compact hydrodynamic radii in intrinsically disordered proteins. Proteins: Structure, Function, and Bioinformatics. Published online December 9, 2016. DOI: 10.1002/prot.25222.

Yarawsky, A. E.; English, L. R.; Whitten, S. T.; Herr, A. B.* The proline/glycine-rich region of the biofilm adhesion protein Aap forms an extended stalk that resists compaction. Journal of Molecular Biology. Published online November 25, 2016. DOI: 10.1016/j.jmb.2016.11.017.

Tomasso, M. E.; Tarver, M. J.; Devarajan, D.; Whitten, S. T.* Hydrodynamic Radii of Intrinsically Disordered Proteins Determined from Experimental Polyproline II Propensities. PLoS Comput Biol 2016, 12(1), e1004686.

Dasari, R.; Masi, M.; Lisy, R.; Ferdérin, M.; English, L. R.; Cimmino, A.; Mathieu, V.; Brenner, A. J.; Kuhn, J. G.; Whitten, S. T.; Evidente, A.; Kiss, R.; Kornienko A.* Fungal metabolite ophiobolin A as a promising anti-glioma agent: In vivo evaluation, structure-activity relationship and unique pyrrolylation of primary amines. Bioorg Med Chem Lett 2015, 25(20), 4544-4548.

Zimmermann, M. T.; Tischer, A.; Whitten, S. T.; Auton, M.* Structural origins of misfolding propensity in the platelet adhesive Von Willebrand Factor A1 domain. Biophys J 2015, 109, 398-406.

Perez, R; Tischer, A.; Auton, M.; Whitten, S. T.* Alanine and proline content modulate global sensitivity to discrete perturbations in disordered proteins. Proteins 2014, 82, 3373-3384.

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 2014, 82, 668-678.

Hilser, V. J.; Whitten, S. T.* Using the COREX/BEST Server to model the native state ensemble. Methods Mol. Biol. 2014, 1084, 255-269.

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.