Mark A. Rould, Ph.D.
Mark earned his PhD in 1991 from Yale, where he solved the first molecular structure of a tRNA synthetase bound to its cognate tRNA, in Tom Steitz’ lab. During his post-doc with Prof Carl Pabo at MIT, he participated in the x-ray crystallographic determination of more than a dozen macromolecular structures, primarily protein-DNA complexes. Mark joined UVM in 1998 to create the Center for X-Ray Crystallography and serve as its first director.
We develop and apply x-ray crystallographic and computational methods to better detect, analyze and optimize the binding of small molecules to target proteins. When optimized for their affinity to a chosen target, these small molecules serve as the starting point, or lead compounds, for pharmaceutical design. Our emphasis is on developing protocols for the rapid identification of lead compounds to challenging targets, such as to protein surfaces that interface with other macromolecules.
Rould MA (1997)  Screening for heavy-atom derivatives and obtaining accurate isomorphous differences. Methods Enzymol 276: 461-472.
Leung JM, Rould MA, Konradt C, Hunter CA, Ward GE (2014) Disruption of TgPHIL1 alters specific parameters of Toxoplasma gondii motility measured in a quantitative, three-dimensional live motility assay. PLoS One 9(1): e85763.
Chen J, Villanueva N, Rould MA, Morrical SW (2010) Insights into the mechanism of Rad51 recombinase from the structure and properties of a filament interface mutant. Nucleic Acids Res 38(14): 4889-906.
Nair UB, Joel PB, Wan Q, Lowey S, Rould MA, Trybus KM (2008) Crystal structures of monomeric actin bound to cytochalasin D. J Mol Biol 384(4): 848-64.
Doublié S, Rould MA (2008) The soul of a new structure-function machine. Structure 16(1): 3-4.
Eckenroth BE, Rould MA, Hondal RJ, Everse SJ (2007) Structural and biochemical studies reveal differences in the catalytic mechanisms of mammalian and Drosophila melanogaster thioredoxin reductases. Biochemistry 46(16): 4694-705.
Aller P, Rould MA, Hogg M, Wallace SS, Doublié S (2007) A structural rationale for stalling of a replicative DNA polymerase at the most common oxidative thymine lesion, thymine glycol. Proc Natl Acad Sci U S A 104(3): 814-8.
Faculty Highlighted Publications
Rould, M.A., Carter, C.W. Jr. (2003) Isomorphous Difference Methods Methods in Enzymology 374, 145-163
Wally J, Halbrooks PJ, Vonrhein C, Rould MA, Everse SJ, Mason AB, Buchanan SK. (2006) The crystal structure of iron-free human serum transferrin provides insight into inter-lobe communication and receptor binding J. Biol. Chem. 281, 24934-44
Rould M.A, Wan Q., Joel P.B., Lowey S., Trybus K.M. (2006) Crystal Structures of Expressed Non-polymerizable Monomeric Actin in the ADP and ATP States J Biol Chem,in press [Epub:doi:10.1074/jbc.M601973200]