Drugging the entire human proteome: Are we there yet?

被引：1

作者：

Smith, Micholas Dean ^{[1
,2
]}

Quarles, L. Darryl ^{[3
,4
]}

Demerdash, Omar ^{[5
]}

Smith, Jeremy C. ^{[1
,2
]}

机构：

[1] Univ Tennessee, Oak Ridge Natl Lab, Ctr Mol Biophys, Oak Ridge, TN 37830 USA

[2] Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA

[3] Univ Tennessee, Hlth Sci Ctr, Dept Med, Memphis, TN 38163 USA

[4] ORRxD LLC, 3404 Olney Dr, Durham, NC 27705 USA

[5] Biosci Div, Oak Ridge Natl Lab, Oak Ridge, TN 37830 USA

来源：

DRUG DISCOVERY TODAY | 2024年 / 29卷 / 03期

关键词：

SCORING FUNCTION; LIGAND INTERACTIONS; ENSEMBLE DOCKING; AFFINITY PREDICTION; BINDING AFFINITIES; CRYO-EM; DESIGN; IMPACT; OPTIMIZATION; FLEXIBILITY;

D O I：

10.1016/j.drudis.2024.103891

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Each of the 20,000 proteins in the human proteome is a potential target for compounds that bind to it and modify its function. The 3D structures of most of these proteins are now available. Here, we discuss the prospects for using these structures to perform proteome-wide virtual HTS (VHTS). We compare physics-based (docking) and AI VHTS approaches, some of which are now being applied with large databases of compounds to thousands of targets. Although preliminary proteome-wide screens are now within our grasp, further methodological developments are expected to improve the accuracy of the results.

引用

页数：10

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