Georgia Research Alliance Eminent Scholar in Computational Structural Biology, Emeritus; Fellow, American Association for the Advancement of Science; Past President, Biophysical Society
My research is aimed at understanding macromolecular structure-function relationships in a variety of biological systems. We incorporate experimental data from collaborations and from the literature into the development of structural and dynamic models. Current areas of interest include:
Virus Structure and Assembly: Understanding how small, icosahedral RNA and DNA viruses assemble should lead to new approaches for the design of antiviral drugs.
My group published a detailed model for satellite tobacco mosaic virus (STMV), using a previously proposed secondary structure model for the genomic RNA. This was the first all-atom model for any virus and represented a significant technical advance. We are now applying those methods to hepatitis B virus (HBV), an extremely important human pathogen. My lab is carrying out experiments to determine the secondary structure of the HBV pregenomic RNA, and we are collaborating with Adam Zlotnick (University of Indiana) in the development of both coarse-grained and all-atom models of HBV at various stages in the viral replication cycle.
My group has also made contributions to our understanding of the packaging of double-stranded DNA into bacteriophage. In particular, we have shown how the packaged DNA conformation depends on the size and shape of the viral capsid, and we have determined the electrostatic, elastic and entropic free energy costs of packaging. Most recently, we have proposed a hypothesis that explains how the packaging motor drives DNA into the virus, and we are beginning detailed modeling studies testing the proposed mechanism.
The Ribosome: As members of the Georgia Tech Center for Ribosomal Origins and Evolution (RiboEvo), my lab is part of a team working to understand key steps in the prebiotic processes that led to the modern ribosome, which catalyzes the translation of mRNA into proteins. We hypothesize that, prior to the development of the genetic code, the ribosome was preceded by a small molecular complex (principally RNA). This putative complex, which we call the "ancestral ribosome", had weak, nonspecific catalytic abilities, and it eventually evolved into the modern RNA-protein translation system. My lab's contributions to this effort include experimental and modeling studies on RNA molecules that comprised the a-ribosome.