使用LoCoMock评分有效筛选脂质双分子层中的蛋白质配体复合物

IF 3 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Rikuri Morita, Yasuteru Shigeta, Ryuhei Harada
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引用次数: 1

摘要

由于膜蛋白在各种生物过程中起着至关重要的作用,它是药物发现的重要靶点。研究两亲分子与膜蛋白的结合姿态对于理解膜蛋白的功能至关重要,对接模拟可以以低计算成本促进蛋白质-配体复合物的筛选。然而,确定配体在非水环境(如脂质双分子层)中的对接姿势是具有挑战性的。为了解决这个问题,我们提出了一个新的对接评分,称为logp校正膜对接(LoCoMock)评分。为了筛选嵌入膜中的假定的蛋白质配体复合物,LoCoMock评分考虑目标配体与膜之间的亲和力。它将蛋白质-配体复合物的对接得分与目标配体的logP结合起来。在使用几种模型配体的演示中,LoCoMock评分比传统的对接评分筛选了更多的假定复合物。作为扩展对接,与传统对接相比,LoCoMock评分可以更有效地筛选膜蛋白作为药物靶点。图形抽象
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Efficient screening of protein-ligand complexes in lipid bilayers using LoCoMock score

Efficient screening of protein-ligand complexes in lipid bilayers using LoCoMock score

Membrane proteins are attractive targets for drug discovery due to their crucial roles in various biological processes. Studying the binding poses of amphipathic molecules to membrane proteins is essential for understanding the functions of membrane proteins and docking simulations can facilitate the screening of protein–ligand complexes at low computational costs. However, identifying docking poses for a ligand in non-aqueous environments such as lipid bilayers can be challenging. To address this issue, we propose a new docking score called logP-corrected membrane docking (LoCoMock) score. To screen putative protein–ligand complexes embedded in a membrane, the LoCoMock score considers the affinity between a target ligand and the membrane. It combines the docking score of the protein–ligand complex with the logP of the target ligand. In demonstrations using several model ligands, the LoCoMock score screened more putative complexes than the conventional docking score. As extended docking, the LoCoMock score makes it possible to screen membrane proteins more effectively as drug targets than the conventional docking.

Graphical abstract

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来源期刊
Journal of Computer-Aided Molecular Design
Journal of Computer-Aided Molecular Design 生物-计算机:跨学科应用
CiteScore
8.00
自引率
8.60%
发文量
56
审稿时长
3 months
期刊介绍: The Journal of Computer-Aided Molecular Design provides a form for disseminating information on both the theory and the application of computer-based methods in the analysis and design of molecules. The scope of the journal encompasses papers which report new and original research and applications in the following areas: - theoretical chemistry; - computational chemistry; - computer and molecular graphics; - molecular modeling; - protein engineering; - drug design; - expert systems; - general structure-property relationships; - molecular dynamics; - chemical database development and usage.
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