Discovery of novel triple helical DNA intercalators by an integrated virtual and actual screening platform.

ABSTRACT: Virtual Screening is an increasingly attractive way to discover new small molecules with potential medicinal value. We introduce a novel strategy that integrates use of the molecular docking software Surflex with experimental validation by the method of competition dialysis. This integrated approach was used to identify ligands that selectively bind to the triplex DNA poly(dA)-[poly(dT)](2). A library containing approximately 2 million ligands was virtually screened to identify compounds with chemical and structural similarity to a known triplex intercalator, the napthylquinoline MHQ-12. Further molecular docking studies using compounds with high structural similarity resulted in two compounds that were then demonstrated by competition dialysis to have a superior affinity and selectivity f

SUBMITTER: Holt PA 

PROVIDER: S-EPMC2651796 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature