On the Mechanism of Gold/NHC Compounds Binding to DNA G-Quadruplexes: Combined Metadynamics and Biophysical Methods
- Authors: Wragg D.; de Almeida A.; Bonsignore R.; Kuhn F.E.; Leoni S.; Casini A.
- Publication year: 2018
- Type: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/576775
Abstract
The binding modes and free-energy landscape of two AuI/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.