Interactions of ligands with macromolecules: Rational design of specific inhibitors of aspartic protease of HIV-1

Abstract

Full Paper: We report here molecular modelling and design study of pseudopeptide inhibitors of the HIV-1 aspartic protease as a therapeutic target for AIDS treatment. A QSAR model was developed for computed enzyme-inhibitor complexation Gibbs free energies and observed enzyme inhibition constants for a training set of potent HIV-1 PR inhibitors. Three inhibitor candidates were found to bind the protease more strongly than ritonavir with binding driven also by hydrophobic forces, which enhances their potential use against drug-resistant protease mutants.