Efficient Screening of Protein-Ligand Complexes in Lipid Bilayers Using LoCoMock Score
Efficient Screening of Protein-Ligand Complexes in Lipid Bilayers Using LoCoMock Score
复制标题
使用 LoCoMock 评分有效筛选脂质双层中的蛋白质-配体复合物
DOI：
10.1007/s10822-023-00502-8
复制
发表时间：
2023
影响因子：
3.5
通讯作者：
Ryuhei Harada
中科院分区：
文献类型：
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作者：
Rikuri Morita;Yasuteru Shigeta;Ryuhei Harada
膜蛋白由于其在各种生物过程中的关键作用而成为药物发现的有吸引力的靶点。研究两亲分子与膜蛋白的结合位姿对于理解膜蛋白的功能是必不可少的，并且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，在非水环境如脂质双层中识别配体的对接姿势可能是具有挑战性的。为了解决这个问题，我们提出了一种新的对接评分，称为logP校正的膜对接（LoCoMock）评分。为了筛选嵌入膜中的推定蛋白质-配体复合物，LoCoMock评分考虑靶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靶配体的logP相结合。在使用几种模型配体的演示中，LoCoMock评分比常规对接评分筛选出更多推定的复合物。作为扩展的对接，LoCoMock评分可以比传统对接更有效地筛选作为药物靶点的膜蛋白。图形摘要
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 logPof 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