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Brian Dominy

Dr. Brian DominyAssociate Professor

Phone: (864) 656-7702
Office: 367 Hunter Laboratories

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, graduating with departmental, college and university honors. He then joined the Scripps Research Institute as a Ralph M. Parsons Foundation predoctoral fellow, earning his Ph.D. in 2001 under the direction of Dr. Charles L. Brooks III. His research involved the development and application of continuum electrostatic models with an emphasis toward understanding the thermodynamic properties of 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. During this time, his research dealt with improving statistical mechanical models, primarily inverse Boltzmann knowledge-based potentials, designed for rapid binding free energy prediction and automated drug design. He joined the faculty of Clemson University in the fall of 2005. In 2010, Dr. Dominy received a National Science Foundation CAREER award to continue his educational and research efforts toward understanding the physical and chemical principles underlying biomolecular evolution.

Research Interests

Dr. Dominy's research involves the development and application of molecular mechanics and bioinformatics techniques to explore the physical chemical basis of biological phenomena at the molecular level. Specifically, the group focuses on applications relevant to medicine, including drug design and biomolecular evolution of drug targets (i.e. drug resistance).

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One of the lab's active research projects involves the exploration of protein evolutionary pathways ending in drug resistance. While advances in the understanding of small molecule / macromolecule interactions have led to successful drug design efforts, it has become evident that bacterial, viral and other types of 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 and chemical “rules” that determine the evolutionary pressures involved in drug resistance. Understanding these pressures involves 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 protein drug targets. As these techniques are developed and improved, it will be possible to construct increasingly accurate evolutionary models capable of predicting the series of mutations that result in drug resistance.

Further, while drug resistance is certainly an important research area in itself, it also represents a useful collection of model systems for studying the broader topic of protein evolution. The process of evolution is often time-consuming, making real-time observation a challenge. Alternatively, drug resistance is an experimentally well-characterized example where the application of a selective pressure upon a quickly reproducing pathogen results in a correspondingly rapid evolutionary adaptation. These examples provide the experimental data upon which theoretical models of biomolecular evolution, developed by Dr. Dominy’s group, may be based. In addition to addressing specific applications in drug resistance, the research performed in Dr. Dominy’s group is also directed toward answering fundamental questions in the field of biomolecular evolution.



Singh MK & Dominy BN (2012) The Evolution of Cefotaximase Activity in the TEM beta-Lactamase. Journal of Molecular Biology 415(1):205-220.

Lee, H. W.; Dominy, B. N.; Cao, W. G., New Family of Deamination Repair Enzymes in Uracil-DNA Glycosylase Superfamily. Journal of Biological Chemistry 2011, 286 (36), 31282-31287.

Singh, M.K., Streu, K., McCrone, A.J., Dominy, B.N. “The Evolution of Catalytic Function in the HIV-1 Protease”, J. Mol. Biol. 408, 792-805, (2011)

Brice, A., Dominy, B.N. “Analyzing the Robustness of the MM/PBSA Free Energy Calculation Method: Applications to DNA Conformational Transitions”, J. Comp. Chem. 32, 1431-1440, (2011)

Singh, M., Dominy, B.N. “Thermodynamic Resolution: How to Errors in Modeled Protein Structures Affect Binding Affinity Predictions?”, Proteins, 78, 1613-1617, (2010)

Lee, H., Brice, A., Dominy, B.N., Cao, W. “Escherichia coli MUG as a Xanthine DNA Glycosylase”, J. Biol. Chem., 285, 41483-41490, (2010)

Mi, R. J.; Dong, L.; Kaulgud, T.; Hackett, K. W.; Dominy, B. N.; Cao, W. G., Insights from Xanthine and Uracil DNA Glycosylase Activities of Bacterial and Human SMUG1: Switching SMUG1 to UDG. Journal of Molecular Biology 2009, 385 (3), 761-778.

Dominy, B. N., Molecular recognition and binding free energy calculations in drug development. Current Pharmaceutical Biotechnology 2008, 9 (2), 87-95.