Binding to the open conformation of HIV-1 protease.

ABSTRACT: A recent crystal structure of HIV-1 protease (HIVp) was the first to experimentally observe a ligand targeting an open-flap conformation. Researchers studying a symmetric pyrrolidine inhibitor found that two ligands cocrystallized with the protease, forcing an unusual configuration and unique crystallographic contacts. One molecule is centered in the traditional binding site (α pose) and the other binds between the flaps (β pose). The ligands stack against each other in a region termed the "eye" site. Ligands bound to the eye site should prevent flap closure, but it is unclear if the pyrrolidine inhibitors or the crystal packing are causing the open state. Molecular dynamics simulations were used to examine the solution-state behavior of three possible binding modes: the ternary complex of

SUBMITTER: Lexa KW 

PROVIDER: S-EPMC3124008 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature