Hydrophobicity Maps of the N-Peptide Coiled Coil of HIV-1 gp41

Blocking HIV-1 viral entry into the host cell offers a promising new strategy for interfering with the HIV-1 life cycle. A major target of inhibitor design is to prevent binding of fusogenic gp41 C-peptides to the trimeric coiled coil of fusion-active N-peptides. Here, we map the hydrophobic charact...

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Bibliographic Details
Published in:Biochemistry (Easton) 2002-03, Vol.41 (9), p.2956-2961
Main Authors: Siebert, Xavier, Hummer, Gerhard
Format: Article
Language:English
Subjects:
HIV Envelope Protein gp41 - chemistry
Information Theory
Models, Molecular
Protein Structure, Secondary
Viral Proteins - chemistry
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Summary:Blocking HIV-1 viral entry into the host cell offers a promising new strategy for interfering with the HIV-1 life cycle. A major target of inhibitor design is to prevent binding of fusogenic gp41 C-peptides to the trimeric coiled coil of fusion-active N-peptides. Here, we map the hydrophobic character of the binding surface of the IQN17 peptide, a soluble analogue of the N-peptide coiled coil. The local binding affinity for a hydrophobic probe is determined by three methods:  a hydrophobic force field, and molecular dynamics in solution analyzed by test particle insertion and inhomogeneous information theory. The regions of highest calculated hydrophobicity overlap with the positions of the hydrophobic anchor residues of the native C-peptides, and of two known inhibitors. Additional binding sites not exploited by these inhibitors are identified, and modifications for enhancing their binding affinity are suggested.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi0158526