Applied theoretical research on AIDS proteins and other molecules of biomedical interest as well as basic research is in progress. Molecular dynamics simulations of AIDS proteins involve projects directly related to the NIH Intramural AIDS Targeted Antiviral Program. The general goal is to understand binding interactions with HIV-1 proteins in order to facilitate the design of drugs which may interfere with the spread of the virus. Important therapeutic targets under study include HIV-1 reverse transcriptase, HIV-1 protease, the HIV-1 envelope protein gp120, and the CD4 receptor protein found on certain host cells. Projects include modeling of leucine zippers in GCN4 and HIV-1 reverse transcriptase, simulations of HIV-1 protease monomer in solution, analysis of CD4 fragments and derivatives, analysis of inhibitor binding to the active site of HIV-1 protease, and investigation of the mechanism of action of HIV-1 protease. Other applied research on molecules of biomedical interest includes using molecular dynamics simulations to predict function or structures of peptides and proteins. Projects include examination of the role of cyclic AMP in the stability and activity of catabolite gene regulatory protein, a molecular dynamics simulation of the L-alanine crystal, and modeling and simulation of winter flounder ice inhibition peptides. Basic research is under way to provide a better understanding of biochemical systems. Projects include studies of environmental effects on protein dynamics, a simulation study of interleukin 1Beta,: comparison with crystallographic and nmr structures, harmonic analysis of large systems, modeling and simulation of lipid bilayers, studies of the B-Z junction of DNA, structural analysis of T4 lysozyme mutants in the harmonic limit, cooperativity of cystine bridge formation in peptides and proteins, comparison of simulations on staphylococcal nuclease with nmr data, and structural characterization of a heme:myoglobin adduct.
