Ligand binding to telomeric G-quadruplex DNA investigated by funnel-metadynamics simulations.

ABSTRACT: G-quadruplexes (G4s) are higher-order DNA structures typically present at promoter regions of genes and telomeres. Here, the G4 formation decreases the replicative DNA at each cell cycle, finally leading to apoptosis. The ability to control this mitotic clock, particularly in cancer cells, is fascinating and passes through a rational understanding of the ligand/G4 interaction. We demonstrate that an accurate description of the ligand/G4 binding mechanism is possible using an innovative free-energy method called funnel-metadynamics (FM), which we have recently developed to investigate ligand/protein interaction. Using FM simulations, we have elucidated the binding mechanism of the anticancer alkaloid berberine to the human telomeric G4 (d[AG₃(T₂AG₃)

SUBMITTER: Moraca F 

PROVIDER: S-EPMC5358390 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature