Targeting Telomeres: Molecular Dynamics and Free Energy Simulation of Gold-Carbene Binding to DNA.

ABSTRACT: DNA sequences in regulatory regions and in telomers at the ends of chromosomes frequently contain tandem repeats of guanine nucleotides that can form stacked structures stabilized by Hoogsten pairing and centrally bound monovalent cations. The replication and elongation of telomeres requires the disruption of these G-quadruplex structures. Hence, drug molecules such as gold (Au)-carbene that stabilize G-quadruplexes may also interfere with the elongation of telomeres and, in turn, could be used to control cell replication and growth. To better understand the molecular mechanism of Au-carbene binding to G-quadruplexes, we employed molecular dynamics simulations and free energy simulations. Whereas very restricted mobility of two Au-carbene ligands was found upon binding as a doublet to one

SUBMITTER: Nayis A 

PROVIDER: S-EPMC7820797 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature