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 π-π 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 r²＝0.79. Based on the predicted binding mode, features of the compounds with higher biological activity were summarized at the end of this article.

Key words: G-quadruplex, quindoline derivative, docking, molecular dynamics, linear interaction energy method