computer-aided approaches for targeting hivgp41针对hivgp41计算机辅助方法.pdfVIP

Biology 2012, 1, 311-338; doi:10.3390/biology1020311 OPEN ACCESS biology ISSN 2079-7737 /journal/biology Review Computer-Aided Approaches for Targeting HIVgp41 William J. Allen 1 and Robert C. Rizzo 1,2,3,* 1 Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA; E-Mail: william.allen@ 2 Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY 11794, USA 3 Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794, USA * Author to whom correspondence should be addressed; E-Mail: rizzorc@; Tel.: +1-631-632-3940; Fax: +1-631-632-8490. Received: 17 July 2012; in revised form: 9 August 2012 / Accepted: 12 August 2012 / Published: 20 August 2012 Abstract: Virus-cell fusion is the primary means by which the human immunodeficiency virus-1 (HIV) delivers its genetic material into the human T-cell host. Fusion is mediated in large part by the viral glycoprotein 41 (gp41) which advances through four distinct conformational states: (i) native, (ii) pre-hairpin intermediate, (iii) fusion active (fusogenic), and (iv) post-fusion. The pre-hairpin intermediate is a particularly attractive step for therapeutic intervention given that gp41 N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) domains are transiently exposed prior to the formation of a six-helix bundle required for fusion. Most peptide-based