Paper Citing NAMD - Abstract
Zhang Chi; Wu Wei-Bin; Lu Yu-Jing; Gu Lian-Quan; Huang Zhi-Shu
Molecular modeling studies of interactions between quindoline derivatives and G-quadruplex
ACTA CHIMICA SINICA, 66:953-958, APR 28 2008
G-quadruplex is a four stranded quadruplex structure in G-rich DNA sequence formed by hydrogen bonds. Inhibition of telomerase by organic compounds that can induce and stabilize the G-quadruplex structure is merging as a new anti-cancer strategy. This article discusses the interaction and binding mode between a series of quindoline derivatives and telomeric G-quadruplex, which may serve as basis of rational design of drugs targeting the G-quadruplex. The interactions of compounds with human telomeric G-quadruplex were simulated by molecular docking and molecular dynamics simulations and their binding free energies were evaluated by a linear interaction energy method. Results showed that the binding of quindoline derivatives and G-quadruplex was maintained by hydrogen bond, aromatic pi-pi stacking, and electrostatic interactions. Terminal substituted groups and length of the side chains are important factors that influence the potency. The predicted binding free energies well correlate the experimental results with r(2) = 0.79. Based on the predicted binding mode, features of the compounds with higher biological activity were summarized at the end of this article.
