Exploration of virtual candidates for human HMG-CoA reductase inhibitors using pharmacophore modeling and molecular dynamics simulations.

ABSTRACT: 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a rate-controlling enzyme in the mevalonate pathway which involved in biosynthesis of cholesterol and other isoprenoids. This enzyme catalyzes the conversion of HMG-CoA to mevalonate and is regarded as a drug target to treat hypercholesterolemia. In this study, ten qualitative pharmacophore models were generated based on chemical features in active inhibitors of HMGR. The generated models were validated using a test set. In a validation process, the best hypothesis was selected based on the statistical parameters and used for virtual screening of chemical databases to find novel lead candidates. The screened compounds were sorted by applying drug-like properties. The compounds that satisfied all drug-like properties were used for mo

SUBMITTER: Son M 

PROVIDER: S-EPMC3875450 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature