"Binding of Anticancer Drug Daunomycin to a TGGGGT G-Quadruplex DNA Probed by All-Atom Molecular Dynamics Simulations: Additional Pure Groove Binding Mode and Implications on Designing More Selective G-Quadruplex Ligands" by Zhanhang Shen

Article

Binding of Anticancer Drug Daunomycin to a TGGGGT G-Quadruplex DNA Probed by All-Atom Molecular Dynamics Simulations: Additional Pure Groove Binding Mode and Implications on Designing More Selective G-Quadruplex Ligands

Journal of Molecular Modeling (2017)

Zhanhang Shen
Kelly A. Mulholland
Yujun Zheng
Dr. Chun Wu, Rowan University

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Abstract

DNA G-quadruplex structures are emerging cancer-specific targets for chemotherapeutics. Ligands that bind to and stabilize DNA G-quadruplexes have the potential to be anti-cancer drugs. Lack of binding selectivity to DNA G-quadruplex over DNA duplex remains a major challenge when attempting to develop G-quadruplex ligands into successful anti-cancer drugs. Thorough understanding of the binding nature of existing non-selective ligands that bind to both DNA quadruplex and DNA duplex will help to address this challenge. Daunomycin and doxorubicin, two commonly used anticancer drugs, are examples of non-selective DNA ligands. In this study, we extended our early all-atom binding simulation studies between doxorubicin and a DNA duplex (d(CGATCG)2) to probe the binding between daunomycin and a parallel DNA quadruplex (d(TGGGGT)4) and DNA duplex. In addition to the end stacking mode, which mimics the mode in the crystal structure, a pure groove binding mode was observed in our free binding simulations. The dynamic and energetic properties of these two binding modes are thoroughly examined, and a detailed comparison is made between DNA quadruplex binding modes and DNA duplex binding modes. Implications on the design of more selective DNA quadruplex ligands are also discussed.

Keywords

anti-cancer drugs,
Molecular dynamics simulation,
DNA quadruplex,
Daunomycin

Disciplines

Medicinal-Pharmaceutical Chemistry

Publication Date

September, 2017

DOI

https://doi.org/10.1007/s00894-017-3417-6

Citation Information

Zhanhang Shen, Kelly A. Mulholland, Yujun Zheng and Chun Wu. "Binding of Anticancer Drug Daunomycin to a TGGGGT G-Quadruplex DNA Probed by All-Atom Molecular Dynamics Simulations: Additional Pure Groove Binding Mode and Implications on Designing More Selective G-Quadruplex Ligands" Journal of Molecular Modeling Vol. 23 Iss. 9 (2017) p. 256
Available at: http://works.bepress.com/chun-wu/6/