The biological importance of G-quadruplexes has recently been confirmed by a high-throughput sequencing of the human genome. Guanine-rich sequences of DNA folded into tetrameric non-Watson-Crick structures are of importance in genes that are located near the replication centers of higher eukaryotes and may play a role in initiating DNA replication and cancer cell proliferation. Therefore, they are considered potentially important targets for anti-cancer drugs that might interfere with the replication process. A series of micro second time scale Molecular Dynamics simulations utilizing the CHARMM36 force field under NPT conditions were carried out on different G-quadruplex structures (with and without incorporated mono-valent metal ions and small drug molecules) to obtain initial structural information about the stability of the these complexes. These simulations indicate that the G-quadruplexes structures are not substantially more stable when bound to the tested drug molecules and no tendency for the bound drug molecules to escape was observed in any of the simulations but the G-quadruplexes unravel if the incorporated mono-valent metal ions are removed.

Molecular dynamics study on the stability of G-quadruplexes in the presents of incorporated mono-valent metal ions and small drug molecules

2019 Fall National Meeting

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