Distinguishing binders from false positives by free energy calculations: fragment screening against the flap site of HIV protease.

ABSTRACT: Molecular docking is a powerful tool used in drug discovery and structural biology for predicting the structures of ligand-receptor complexes. However, the accuracy of docking calculations can be limited by factors such as the neglect of protein reorganization in the scoring function; as a result, ligand screening can produce a high rate of false positive hits. Although absolute binding free energy methods still have difficulty in accurately rank-ordering binders, we believe that they can be fruitfully employed to distinguish binders from nonbinders and reduce the false positive rate. Here we study a set of ligands that dock favorably to a newly discovered, potentially allosteric site on the flap of HIV-1 protease. Fragment binding to this site stabilizes a closed form of protease, which c

SUBMITTER: Deng N 

PROVIDER: S-EPMC4306491 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature