Paramagnetic relaxation assisted docking of a small indole compound in the HIV-1 gp41 hydrophobic pocket.

ABSTRACT: The hydrophobic pocket contained within the gp41 coiled coil is an important target for small molecules designed to inhibit HIV-1 fusion. While various screening experiments have identified molecules purported to bind in this pocket, few have confirmed details of the interaction, instead relying on computational docking to predict the binding mode. This is made more challenging by the fact that residues lining the hydrophobic pocket are highly flexible, as is typical for a protein-protein interaction site, limiting the predictive power of computational tools. In this study, we report on an NMR method to define the binding mode of 1-5i, a compound in a series of newly developed indole inhibitors. We show that paramagnetic relaxation enhancement of ligand protons due to an MTSL group positio

SUBMITTER: Gochin M 

PROVIDER: S-EPMC3060958 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature