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Thomas C. Jenkins
Department of Biophysics
110 Jenkins Hall
3400 N. Charles Street
Baltimore, MD 21218

410-516-7245 phone
410-516-4118 fax


Dr. Peter Privalov
Joint-Appointed Faculty
Professor, Biology

Johns Hopkins University
Department of Biology
3400 North Charles Street
121 Mudd Hall
Baltimore, MD 21218
410-516-6532 Office
410-516-5213 Fax
pprival1@jhu.edu

Physical Basis of Structure of Biological Macromolecules

We are interested in physical principles of the architecture of biological macromolecules, proteins, nucleic acids and their complexes. This includes understanding of the energetic basis of these molecular structures, of the forces responsible for folding of polymeric molecules in aqueous media into unique three-dimensional structures and their association with the partner. Recognition of the partners and changes resulting from their interaction is actually the most fundamental biological function displayed on the molecular level.

Solution of the above problems requires experimental studies of the changes of biological macromolecules, their mutants and synthetic analogs induced by various external conditions, or by association with the partners and ligands. These processes are studied by various physical methods, and first of all by calorimetry, which provides direct information on the energies involved in the observed processes. The heat effects of intra- and inter-molecular processes studied in dilute solutions are usually extremely small. Therefore to measure these effects we had to develop special supersensitive microcalorimetric methods which are widely used now all over the world. The methodology of our research consists of finding correlations between the obtained structural and energetic information, computer simulation of the studied processes, design of synthetic models and their experimental verification.

Selected Publications:

  • Privalov, P.L., A.I. Dragan, C. Crane-Robinson, K.J. Breslauer, D.P. Remeta, C.A.S.A. Minetti. (2007) What drives proteins into the major and minor grooves of DNA?  J. Mol. Biol. 365:1-9.
  • Privalov, P.L., and A.I. Dragan. (2007) Microcalorimetry of biological macromolecules. Biophys. Chem. 126:16-24.
  • Dragan, A.I., V.V. Hargreaves, E.N. Makeyeva, and P.L. Privalov. (2007) Mechanism of activation of the interferon regulator factor-3: the role of C-terminal domain phosphorylation in IRF-3 dimerization and DNA binding. Nucleic Acids Res. 35:3525-3534.
  • Dragan, A.I., Z. Li, E.N. Makeyeva, E.I. Milgotina, Y. Liu, C. Crane-Robinson, and P.L. Privalov. (2006) The forces driving the binding of homeodomains to DNA. Biochemistry 45:141-151.
  • Crane-Robinson, C., A.I. Dragan, and P.L. Privalov. (2006) The extended arms of DNA-binding domains: a tail of tails. Trends Biochem. Sci. 31:547-552.
  • Hargreaves, V., A.I. Dragan, E.N. Makeyeva, and P.L. Privalov. (2005) Stability and DNA binding ability of the N-terminal domains of IRFs. Biochemistry 44:14202-14209.
  • Dragan, A.I., L. Frank, Y. Liu, E.N. Makeyeva, C. Crane-Robonsin, and P.L. Privalov. (2004) Thermodynamic signature of GCN4-bZIP binding to DNA indicates the role of water in discriminating between the AP-1 and ATF/CREB sites. J. Mol. Biol. 343:865-878.
  • Dragan, A.I., C.M. Read, E.N. Makeyeva, E.I. Milgotina, M.E. Churchill, C. Crane-Robinson, and P.L. Privalov. (2004) DNA binding and bending by HMG boxes: energetic determinants of specificity. J. Mol. Biol. 343:371-393.

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