The Science and Art of Structure-Based Virtual Screening

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL ACS Medicinal Chemistry Letters Pub Date : 2024-03-25 DOI:10.1021/acsmedchemlett.4c00093

Hongtao Zhao*,

引用次数: 0

Abstract

Structure-based virtual screening has gained momentum again as the high attrition rate at every stage of drug discovery drives the need to explore a greater chemical space. From the Bayesian perspective, its shortcomings as a viable strategy for sustainable hit discovery are discussed, with regard to the prior hit rates of screening libraries and the performance of computational methods. Lessons are shared in selecting virtual hits for experimental validation learned from a series of eight successful campaigns, one of which impacted the discovery of a drug candidate currently in clinical trials.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

基于结构的虚拟筛选的科学与艺术

由于药物发现各个阶段的高损耗率促使人们需要探索更大的化学空间，基于结构的虚拟筛选再次获得了发展势头。从贝叶斯的角度来看，虚拟筛选作为一种可持续发现新药的可行策略，在筛选文库的先验命中率和计算方法的性能方面存在不足。此外，还分享了从一系列八次成功活动中总结出的选择虚拟命中进行实验验证的经验，其中一次活动对目前正在进行临床试验的候选药物的发现产生了影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.