6533b830fe1ef96bd1297057
RESEARCH PRODUCT
On the Mechanism of Gold/NHC Compounds Binding to DNA G-Quadruplexes: Combined Metadynamics and Biophysical Methods
Stefano LeoniAngela CasiniAngela CasiniFritz E. KühnDarren WraggAndreia De AlmeidaRiccardo Bonsignoresubject
Molecular Structure010405 organic chemistryIn silicoMetadynamicsDrug designSequence (biology)General MedicineDNAGeneral Chemistryanticancer010402 general chemistryG-quadruplex01 natural sciencesCombinatorial chemistryCatalysis0104 chemical sciencesG-Quadruplexeschemistry.chemical_compoundNucleic acid thermodynamicsFörster resonance energy transferchemistryFluorescence Resonance Energy TransferN-heterocyclic carbenesGoldDNAdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-07-25 | Angewandte Chemie International Edition |