Vincent J. Hilser, Ph.D.
ProfessorDr. Hilser

Telephone: (409) 747-6813
Fax: (409) 772-6334
E-mail:vjhilser@utmb.edu
Campus Location: 5.104B Medical Research Building
Mail Route: 1068
Laboratory Web Page

Research

DHFR
Energetic connectivities in DHFR reveal regions that become more dynamic when binding occurs at the folate site.
(From Pan, H., Lee, J.C. and Hilser, V.J. (2000) PNAS)

Although proteins and other biological macromolecules are often modeled as unique structures, it is well-known that these structures are dynamic interconverting ensembles of conformations. This dynamic behavior is both affected and affects the biological function. To address the impact of conformational heterogeneity (i.e. dynamics) on the biophysical properties and functions of proteins, we developed a theoretical approach that models proteins as large ensembles of conformations (Hilser, V.J., and E. Freire. (1996) J. Mol. Biol. 262: 756-772). This theoretical approach has allowed us to develop an experimental strategy for dissecting the contributions of dynamics to molecular recognition. In addressing molecular recognition, we have begun studying the interaction of SEM5 with its putative recognition sequence on the Sos protein. Both proteins are key players in the Ras signaling cascade. We are studying the SEM5/Sos association using various biophysical methods designed to characterize the structural and energetic features of the binding process (e.g. titration and scanning calorimetry, NMR, X-ray crystallography, CD, and fluorescence spectroscopy). Our goal is to quantitatively account for the effects of dynamics so that we can bring this information to bear on a broad spectrum of more complex biological problems including allosterism, signal tranduction and protein folding. In addition to our experimental efforts, our lab has various computational projects. We have been involved with the development of computational tools designed to apply our ensemble-based approach toward allosterism (Pan, H., et al. (2000) Proc. Nat. Acad. Sci. USA 97, 12020-12025) and protein fold recognition (Wrabl, J.O., et al. (2001) Protein Sci. 10, 1032-1045.