Binding of Telomestatin, TMPyP4, BSU6037, and BRACO19 to a Telomeric G-Quadruplex-Duplex Hybrid Probed by All-Atom Molecular Dynamics Simulations with Explicit Solvent.

ABSTRACT: A promising anticancer therapeutic strategy is the stabilization of telomeric G-quadruplexes using G-quadruplex-binding small molecules. Although many G-quadruplex-specific ligands have been developed, their low potency and selectivity to G-quadruplexes over duplex remains unsolved. Recently, a crystal structure of a telomeric 3' quadruplex-duplex hybrid was reported and the quadruplex-duplex interface was suggested to a good target to address the issues. However, there are no high-resolution complex structures reported for G-quadruplex ligands except for a docked BSU6037. In this study, molecular dynamic (MD) binding simulations with a free ligand were used to study binding poses and dynamics of four representative ligands: telomestatin, TMPyP4, BSU6037, and BRACO19. The MD data showed th

SUBMITTER: Sullivan HJ 

PROVIDER: S-EPMC6289566 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature