Angewandte Chemie International Edition · 2018 · 76 citations · 27 references
Natural SciencesBiochemistryChemistryBiophysical ChemistryDrug DesignDrug DiscoveryBiomolecular InteractionsCarbene ComplexesLigand BindingMolecular DynamicsMolecular ModelingProtein-ligand BindingBindersG-quadruplex Ligand BindingG-quadruplex Molecular DynamicsG-quadruplex ThermodynamicsG-quadruplex-protein InteractionsPromoter Sequence MotifsRational DesignTelomeric Repeats
/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.
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