Brian Dominy
Assistant Professor
Phone: (864) 656-7702
Office: 367 Hunter Laboratories
E-mail: dominy@clemson.edu
Research Interests | Publications
Dr. Dominy earned his B.S. degree in 1995 from Carnegie Mellon University in biological sciences / computer science track with a minor in chemistry. He earned his Ph.D. at the Scripps Research Institute in 2001 working with Dr. Charles Brooks III. His dissertation focused on clarifying the role of electrostatics in the stability and dynamics of mesophilic and extremophilic proteins. From 2002 to 2005 he worked as an NIH postdoctoral fellow at Harvard University with Dr. Eugene Shakhnovich in the department of Chemistry and Chemical Biology. Here, his work dealt with improving statistical methods, primarily Boltzmann weighted knowledge-based potentials, for fast binding energy prediction and automated drug design. He joined the faculty at Clemson University in the fall of 2005.
Research Interests
Dr. Dominy's research utilizes computational methods, including physical modeling and statistical approaches, to explore the physical chemical basis of biological phenomena at the molecular level. Specifically, the group focuses on topics relevant to medicine, including drug design, drug resistance, viral capsid assembly, and related areas.
One active research project involves the exploration of protein evolutionary pathways toward drug resistance. While advances in the understanding of small molecule / macromolecule interactions have led to successful drug design efforts, it has become evident that both bacterial and viral pathogens are not static targets. Instead, they continually evolve and become resistant to current therapies. It is a goal of Dr. Dominy’s group to understand the physical basis behind the evolutionary pressures involved in process of drug resistance. Understanding these pressures will involve modeling the effect of mutations on the binding efficacy of inhibitors/drugs as well as modeling the effect of mutations on the natural activity of the drug targets. As these techniques are developed and improved, it will be possible to construct increasingly accurate evolutionary models that describe the physical basis underlying the biological process of evolving drug resistance.
Further, while drug resistance is certainly an important topic in itself, it also represents a useful model system for studying protein evolution. Drug resistance is an experimentally well-characterized example of introducing a perturbation into the environment of quickly evolving organisms and the correspondingly rapid evolutionary adaptation. It is hoped that this research will also shed some light on some fundamental questions in protein evolution as physically meaningful (and experimentally verifiable) evolutionary landscapes are developed.
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Publications
Dominy, B.N., Minoux, H., Brooks, C.L. III. (2004), The Electrostatic Basis for Thermophilic Protein Stability, Proteins: Structure, Function, and Bioinformatics. 57, 128-141.
Dominy, B.N., Shakhnovich, E.I. (2004), A Physical Motivation for Knowledge-Based Potentials: Application to Binding Free Energy Prediction, J. Med. Chem. 47, 4538-4558.
Liu, Z., Dominy, B.N., Shakhnovich, E.I. (2004), Distance-Dependent Potential for Peptide Docking, J. Am. Chem. Soc. 126, 8515-8526.
Dominy, B.N., Brooks, C.L. III (2002) Salt Effects and Protein Stability: The Cold-Shock Protein Family. J. Mol. Biol., 319, 541-554
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