Present Position and Address

MRB 6.136B
Mail Route:1079
Telephone: (409) 772-2178
Fax: (409) 747-8608
Email: bdodson@scms.utmb.edu

B.A. 1965 University of Texas, Austin
Ph.D. 1970 University of Texas, Houston

RESEARCH INTERESTS:

My research interests lie in enzyme reaction mechanisms, their description and elucidation and, in particular, computational methods to model them. These interests naturally lead to two areas of computational
biochemistry:

(a) Modeling the chemical steps in enzyme mechanisms and determining the effect of enzyme active site environments on those steps.

(b) The analysis of kinetic models of enzyme reactions and the quantitative determination of the parameters of those models by fitting them to experimental data, including error analysis for the fitted parameters.

An example project deriving from these research interests:

The chemistry of enzyme-catalyzed reactions and the influence of enzyme active site environment on the details of those reactions. The T4 Endonuclease V base excision repair glycosylase reaction is being modeled by a combination of molecular dynamics and quantum chemistry calculations. Several important aspects of this mechanism have been refractory to experimental determination. It is hoped that choices between several mechanistic alternatives can be guided by the computational methods. This methodology can also be applied to the glycosylase reactions catalyzed by other DNA base excision repair glycosylases, in particular, E. coli MutY. Enzymes were chosen for this research program because high resolution (1.1-1.4 Angstrom) crystal structures were available for them, their mutants, and for mechanistically important enzyme-inhibitor and mutant enzyme-substrate complexes.

RECENT PUBLICATIONS:

1. Raymond C. Manuel, Kenichi Hitomi, Andrew S. Arvai, Paul G. House, Andrew J. Kurtz, M. L. Dodson, Amanda K. McCullough, John A. Tainer, and R. Stephen Lloyd. Reaction intermediates in the catalytic mechanism of Escherichia coli MutY DNA glycosylase. J. Biol. Chem., 279:46930-46939, 2004.
2. Meador, M. G., Rajagopalan, L., Lloyd, R. Stephen, and Dodson, M. L. Role of His16 in Turnover of T4 Pyrimidine Dimer Glycosylase. J. Biol. Chem., 279:3348-3353, 2004.
3. Andrew J. Kurtz, M. L. Dodson, and R. Stephen Lloyd. Evidence for Multiple Imino Intermediates and Identification of Reactive Nucleophiles in Peptide-Catalyzed beta-Elimination at Abasic Sites. Biochemistry, 41:7054-7064, 2002.
4. Sarah Burgess, Pawel Jaruga, M. L. Dodson, Miral Dizdaroglu, and R. Stephen Lloyd. Determination of Active Site Residues of Escherichia coli Endonuclease VIII. J. Biol. Chem., 277:2938-2944, 2002.

5. M. L. Dodson and R. Stephen Lloyd. Mechanistic comparisons among base excision repair glycosylases. Free Radical Biology and Medicine, 32:678-682, 2002.
6. M. L. Dodson, Andrew J. Kurtz, and R. Stephen Lloyd. T4 Endonuclease V: Use of NMR and Borohydride Trapping to Provide Evidence for Covalent Enzyme-Substrate Imine Intermediate. In: Methods in Enzymology. Academic Press, 354:202-207, 2002.