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Biology 2012, 1(2), 311-338; doi:10.3390/biology1020311
Review

Computer-Aided Approaches for Targeting HIVgp41

1
 and 1,2,3,*
Received: 17 July 2012; in revised form: 9 August 2012 / Accepted: 12 August 2012 / Published: 20 August 2012
(This article belongs to the Special Issue Structural and Molecular Biology of HIV)
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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 inhibitors, including the FDA‑approved drug T20, target the intermediate and there are significant efforts to develop small molecule alternatives. Here, we review current approaches to studying interactions of inhibitors with gp41 with an emphasis on atomic-level computer modeling methods including molecular dynamics, free energy analysis, and docking. Atomistic modeling yields a unique level of structural and energetic detail, complementary to experimental approaches, which will be important for the design of improved next generation anti-HIV drugs.
Keywords: HIV; AIDS; gp41; T20; structural biology; structure-based drug design; computer-aided drug design; molecular dynamics; docking; DOCK HIV; AIDS; gp41; T20; structural biology; structure-based drug design; computer-aided drug design; molecular dynamics; docking; DOCK
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Allen, W.J.; Rizzo, R.C. Computer-Aided Approaches for Targeting HIVgp41. Biology 2012, 1, 311-338.

AMA Style

Allen WJ, Rizzo RC. Computer-Aided Approaches for Targeting HIVgp41. Biology. 2012; 1(2):311-338.

Chicago/Turabian Style

Allen, William J.; Rizzo, Robert C. 2012. "Computer-Aided Approaches for Targeting HIVgp41." Biology 1, no. 2: 311-338.


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