On the Mechanism of Gold/NHC Compounds Binding to DNA G-Quadruplexes: Combined Metadynamics and Biophysical Methods.
Darren WraggAndreia de AlmeidaRiccardo BonsignoreFritz E KühnStefano LeoniAngela CasiniPublished in: Angewandte Chemie (International ed. in English) (2018)
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.
Keyphrases
- dna binding
- single molecule
- transcription factor
- circulating tumor
- high resolution
- cell free
- endothelial cells
- dna methylation
- high throughput
- silver nanoparticles
- gene expression
- induced pluripotent stem cells
- living cells
- molecular docking
- single cell
- nucleic acid
- fluorescent probe
- dna damage response
- emergency department
- circulating tumor cells
- amino acid
- binding protein
- mass spectrometry
- energy transfer
- dna damage
- molecular dynamics simulations