Molecular dynamics study of binding of isoquinoline alkaloids to G-quadruplex

ZHANG Bo; HE Yiran; LIU Yingchun; WANG Qi

doi:10.11949/0438-1157.20191265

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Molecular dynamics study of binding of isoquinoline alkaloids to G-quadruplex

Biochemical engineering and technology | 更新时间：2026-07-24

- Molecular dynamics study of binding of isoquinoline alkaloids to G-quadruplex
- CIESC Journal Vol. 71, Issue 1, Pages: 344-353(2020)
- 作者机构：
  
  浙江大学化学系，浙江杭州310027
- 作者简介：
- 基金信息：
- DOI：10.11949/0438-1157.20191265
  CLC： O 641.3
- Received：24 October 2019，
  
  Revised：2019-11-07，
  
  Online First：12 August 2020，
  
  Published：05 January 2020
- 稿件说明：
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张博, 何依然, 刘迎春, 王琦. 异喹啉类生物碱和G-四链体结合的分子动力学研究[J]. 化工学报, 2020, 71(1): 344-353

ZHANG Bo, HE Yiran, LIU Yingchun, WANG Qi. Molecular dynamics study of binding of isoquinoline alkaloids to G-quadruplex[J]. CIESC Journal, 2020, 71(1): 344-353
张博, 何依然, 刘迎春, 王琦. 异喹啉类生物碱和G-四链体结合的分子动力学研究[J]. 化工学报, 2020, 71(1): 344-353 DOI： 10.11949/0438-1157.20191265.

ZHANG Bo, HE Yiran, LIU Yingchun, WANG Qi. Molecular dynamics study of binding of isoquinoline alkaloids to G-quadruplex[J]. CIESC Journal, 2020, 71(1): 344-353 DOI： 10.11949/0438-1157.20191265.

摘要

G-四链体是核酸的一种非经典二级结构，主要出现于富含鸟嘌呤（G）碱基的DNA或RNA序列。生物体内的G-四链体主要形成于端粒区域和某些原癌基因的启动子区域，是生物医学研究的重要对象。以G-四链体作为靶点的抗癌策略虽被多次提出，但目前还未有成功进入临床试验的案例。因此，有关原癌基因启动子区域的G-四链体与配体结合的研究，可以对靶向抗癌药物的设计提供指导性建议。使用分子动力学模拟的方法，研究了不同的异喹啉类生物碱与G-四链体的结合机理。通过考察四种异喹啉配体与G-四链体结合的过程，得到了异喹啉配体与G-四链体稳定结合的构象以及结合的主导因素。此工作从原子分子层面深化了对异喹啉类生物碱和G-四链体结合机理的微观认识，对抗癌药物设计具有指导意义。

Abstract

G-quadruplex is a nonclassical secondary structure of nucleic acids

which is mainly found in guanine (G) - rich DNA or RNA sequences. The G-quadruplex in organism is mainly formed in the telomere region and the promoter region of some proto-oncogenes

which is an essential object of biomedical research. Although the anti-cancer strategy targeting G-quadruplex has been proposed many times

no successful clinical trials have been conducted so far. Therefore

the study of G-quadruplex ligand binding in the proto-oncogene promoter region can provide guiding suggestions for the design of targeted anti-cancer drugs. The binding mechanism of different isoquinoline alkaloids to G-quadruplex was studied by molecular dynamics simulation. The confirmation of the stable binding of four isoquinoline ligands to G-quadruplex and the dominant factors of the binding were obtained by studying the binding process of the four isoquinoline ligands to G-quadruplex. This work has deepened the microscopic understanding of the binding mechanism of isoquinoline alkaloids and G-quadruplex at the atomic and molecular level and has guiding significance for the design of anti-cancer drugs.

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