Computational analysis of HIVgp41 mutants in complex with peptide based fusion inhibitors

COMP 219

Brian Edward McGillick, mcgillick_brian@yahoo.com1, Trent E. Balius, tbalius@ams.sunysb.edu2, Sudipto Mukherjee, sudipto.mukherjee@gmail.com2, and Robert C. Rizzo, rizzorc@gmail.com2. (1) Department of Biomedical Engineering, Stony Brook University, Health Sciences Center, T18, Room 030, Stony Brook, NY 11794, (2) Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11790-3600
The viral protein gp41 mediates fusion of the viral envelope with the host cell membrane during infection by HIV. The potential to halt the fusion event, thus interrupting the viral life cycle, has made gp41 an attractive drug target. Currently, there are two entry inhibitors approved by the FDA including the peptide-based inhibitor T20 (Fuzeon) which targets gp41. Despite T20's importance as the first entry inhibitor of this class, experimentally determined s-tructural information on binding has not yet been reported. Thus, the origins of drug resistance which arise from use of T20 are unknown. In this study, structural models of gp41 in complex with T20 have been constructed, which are embedded into an explicit lipid bilayer, and all-atom molecular dynamics simulations were used in an effort to characterize binding in this system. The goal is to deduce the origins of resistance to clinically relevant gp41 mutants.

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009