On the Mechanism of Gold/NHC Compounds Binding to DNA G‐Quadruplexes: Combined Metadynamics and Biophysical Methods

Abstract

Abstract The binding modes and free‐energy landscape of two Au I /N‐heterocyclic carbene complexes interacting with G‐quadruplexes, namely a human telomeric (hTelo) and a promoter sequence ( C‐KIT1 ), are studied here for the first time by metadynamics. The theoretical results are validated by FRET DNA melting assays and provide an accurate estimate of the absolute gold complex/DNA binding free energy. This advanced in silico approach is valuable to achieve rational drug design of selective G4 binders.