麻醉药物研发中的计算机模拟方法：计算机辅助药物设计

Insilico Approaches in Anesthetic Drug Development: Computer Aided Drug Designing.

作者信息

Peng Q-X, Guan X-H, Yi Z-G, Su Y-P

机构信息

Department of Anesthesiology, The First Hospital of Changsha, Changsha, China.

出版信息

Drug Res (Stuttg). 2015 Nov;65(11):587-91. doi: 10.1055/s-0034-1395564. Epub 2014 Dec 2.

DOI:10.1055/s-0034-1395564

PMID:25463595

Abstract

OBJECTIVE

Computer Aided Drug DESIGNing is fast becoming an important tool in Drug discovery, and in the field of anesthetic drug development we are the first to use in silico approaches to look for novel anesthetic compounds.

DESIGN

The approach of molecular modeling, Virtual screening, Drug-likeness, molecular docking and molecular dynamics simulations (MDS) was employed for this study.

RESULT

Our approach of virtual screening Drug-likeness, adsorption, distribution, metabolism, excretion and toxicity analysis of around 50 000 compounds from Inter Bio Screen (IBS) Database have given us top 5 Lead compounds against ASN289 of γ-aminobutyric acid (GABAA) receptor, a common target of known anesthetic compounds. Out of the top 5 Lead compounds one (Lead 5) was selected for further MDS analysis based on its Binding free energy and number of physical interactions with GABAA.

CONCLUSION

The MDS analysis of Lead 5 reveals the complex to be stable and thus suitable for further in vitro and in vivo analysis.

摘要

目的

计算机辅助药物设计正迅速成为药物研发中的一项重要工具，在麻醉药物开发领域，我们率先使用计算机模拟方法来寻找新型麻醉化合物。

设计

本研究采用分子建模、虚拟筛选、类药性、分子对接和分子动力学模拟（MDS）方法。

结果

我们对来自国际生物筛选（IBS）数据库的约50000种化合物进行虚拟筛选、类药性、吸收、分布、代谢、排泄和毒性分析的方法，为我们提供了针对γ-氨基丁酸（GABAA）受体ASN289的前5种先导化合物，GABAA受体是已知麻醉化合物的常见靶点。基于其与GABAA的结合自由能和物理相互作用数量，从这5种先导化合物中选择了一种（先导化合物5）进行进一步的MDS分析。