Center for Molecular Biophysics & Biophysical Chemistry

Edward Arnold
Professor of Chemistry, Rutgers University
(732) 235-5323
Center for Advanced Biotechnology and Medicine, Room 016

Dr. Arnold and his group are concentrating on using structural information about viruses to guide antiviral drug and vaccine design. In pursuit of this goal, the laboratory is applying a combination of X-ray crystallography, molecular biology, virology, protein biochemistry, and molecular modeling to the study of problems that are of both fundamental and applied interest.

One of the major projects in the laboratory is the biochemical and crystallographic study of HIV reverse transcriptase (RT), in collaboration with Dr. Stephen Hughes at the NCI-FCRDC in Frederick, MD. The team has solved the three-dimensional structures of HIV-1 RT in complex with a double-stranded DNA template-primer, with numerous small-molecule inhibitors, and without any bound ligand. Among the structures that are currently being determined are HIV-1 RT complexed with RNA/DNA template-primers and drug-resistant variants of HIV-1 RT complexed with inhibitors. These studies are yielding numerous novel insights into polymerase structure-function relationships, detailed mechanisms of drug resistance, and structure-based design of RT inhibitors.

Another major project in the laboratory, co-directed by Dr. Gail Ferstandig Arnold, consists of combinatorial engineering of human rhinoviruses to display immunogens from more dangerous pathogens for the purpose of developing vaccines against these pathogens. Libraries of chimeric viruses are generated and immunoselected to optimize the isolation of viruses with the most effectively reconstructed foreign immunogens. Rhinovirus:HIV-1 constructs have been made that elicit antibodies (in guinea pigs) capable of potentially neutralizing HIV-1 in cell culture. Some are currently being tested in chimpanzees. The Arnold Lab group is analyzing the structures of rhinovirus chimeras using X-ray crystallography, with the long-term objectives of determining three-dimensional correlates of immunogenicity and developing a structural basis for design of more effective human vaccines. Work in the laboratory also includes structural studies of other picornaviruses, HIV-1 integrase, and other polymerases including cellular RNA polymerases and their associated transcription factors.