Next Article in Journal / Special Issue
Transcriptional Gene Silencing (TGS) via the RNAi Machinery in HIV-1 Infections
Previous Article in Journal
Analyzing the microRNA Transcriptome in Plants Using Deep Sequencing Data
Previous Article in Special Issue
HIV-1 Tat Binding to PCAF Bromodomain: Structural Determinants from Computational Methods
Biology 2012, 1(2), 311-338; doi:10.3390/biology1020311

Computer-Aided Approaches for Targeting HIVgp41

Received: 17 July 2012 / Revised: 9 August 2012 / Accepted: 12 August 2012 / Published: 20 August 2012
(This article belongs to the Special Issue Structural and Molecular Biology of HIV)
View Full-Text   |   Download PDF [848 KB, uploaded 20 August 2012]   |   Browse Figures


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.

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
MDPI and ACS Style

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

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


Cited By

[Return to top]
Biology EISSN 2079-7737 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert