Binding of BRACO19 to a Telomeric G-Quadruplex DNA Probed by All-Atom Molecular Dynamics Simulations with Explicit Solvent.

ABSTRACT: Although BRACO19 is a potent G-quadruplex binder, its potential for clinical usage is hindered by its low selectivity towards DNA G-quadruplex over duplex. High-resolution structures of BRACO19 in complex with neither single-stranded telomeric DNA G-quadruplexes nor B-DNA duplex are available. In this study, the binding pathway of BRACO19 was probed by 27.5 µs molecular dynamics binding simulations with a free ligand (BRACO19) to a DNA duplex and three different topological folds of the human telomeric DNA G-quadruplex (parallel, anti-parallel and hybrid). The most stable binding modes were identified as end stacking and groove binding for the DNA G-quadruplexes and duplex, respectively. Among the three G-quadruplex topologies, the MM-GBSA binding energy analysis suggested that BRACO19's b

SUBMITTER: Machireddy B 

PROVIDER: S-EPMC6471034 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature