Although compounds designed by computer-aided drug design (CADD) have been successfully used in the clinic, drug design efforts on HIV-1 IN inhibitors have almost exclusively relied on classic medicinal chemistry techniques. With the recent availability of high quality structures of the catalytic domain of HIV-1 IN, computer-aided drug design studies are becoming feasible. The long-tern goal of this research project is the computer-aided design of lead compounds for inhibition of HIV-1 integrase, the newest enzymatic target for AIDS therapeutics.
Two specific aims to be addressed in this proposed work are: 1) Identify binding sites for inhibitors and obtain computational models of complexes of HIV-1 integrase catalytic domain with inhibitors. 2) Search for potential leads based on the models created in the first part of the project and refine good leads with more sophisticated methods.
| Schames, Julie R; Henchman, Richard H; Siegel, Jay S et al. (2004) Discovery of a novel binding trench in HIV integrase. J Med Chem 47:1879-81 |
| Rowley, David C; Hansen, Mark S T; Rhodes, Denise et al. (2002) Thalassiolins A-C: new marine-derived inhibitors of HIV cDNA integrase. Bioorg Med Chem 10:3619-25 |
| Ni, H; Sotriffer, C A; McCammon, J A (2001) Ordered water and ligand mobility in the HIV-1 integrase-5CITEP complex: a molecular dynamics study. J Med Chem 44:3043-7 |
| Sotriffer, C A; Ni, H; McCammon, J A (2000) Active site binding modes of HIV-1 integrase inhibitors. J Med Chem 43:4109-17 |
