基于虚拟筛选从中药中发现高选择性靶向DDX3X抑制剂
Discovery of Highly Selective DDX3X Inhibitors from Traditional Chinese Medicine based on Virtual Screening
邵晨 1宋昱 2史学伟 3王宝珍 1武靖 1董志强1
作者信息
- 1. 内蒙古科技大学包头医学院第一附属医院药物临床研究室,包头 014010
- 2. 日本富山大学放射线肿瘤学部门,日本 930-0194
- 3. 内蒙古科技大学包头医学院第一附属医院肿瘤外科,包头 014010
- 折叠
摘要
目的 基于虚拟筛选从中药中发现高选择性靶向DDX3X抑制剂.方法 基于对DDX3X 蛋白解旋酶上一段独特基因序列分析,构建出选择性位点,针对该选择性位点从中药数据库中筛选出高选择性的 DDX3X 蛋白解旋酶抑制剂.通过分子对接、互作模式分析以及计算自由结合能的方法筛选出具有潜在抑制活力的 DDX3X 抑制剂,并对活性位点的构效关系进行分析.结果 最终筛选得到 4 个化合物(ZINC4096316、ZINC33861462、ZINC67903526、ZINC85530944)可作为潜在的DDX3X蛋白解旋酶抑制剂.结论 基于DDX3X蛋白解旋酶上一段独特的基序构建选择性位点并筛选选择性抑制剂,对DDX3X蛋白解旋酶强效选择性抑制剂研发具有一定的指导意义.
Abstract
Objective To discover highly selective targeting DDX3X inhibitors from traditional Chinese medicine based on virtual screening.Methods Based on the unique gene sequence analysis of DDX3X protein helicase,a selective site was constructed and highly selective DDX3X protein helicase inhibitors were screened from the Chinese traditional medicine database.The potential inhibitors of DDX3X were screened by molecular docking,interaction pattern analysis and free binding energy calculation,and the structure-activity relationship of active sites was analyzed.Results Four compounds(ZINC4096316,ZINC33861462,ZINC67903526,ZINC85530944)were screened as potential inhibitors of DDX3X.Conclusion This study is based on a unique motif of DDX3X to construct selective sites and screen selective inhibitors,which has a certain guiding significance for the strong selective inhibitors of DDX3X.
关键词
DDX3X抑制剂/人类免疫缺陷病毒1/型/分子对接/虚拟筛选/自由结合能Key words
DDX3X inhibitor/HIV-1/Molecular docking/Virtual screening/Free binding energy引用本文复制引用
基金项目
内蒙古自治区高等学校科学技术研究项目(NJZY22071)
出版年
2024
国家科技期刊平台
NSTL
万方数据