PD-1/PD-L1 复合物抑制剂结合模式的分子建模研究。
Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors.
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6125, USA.
Department of Chemistry, University of Nebraska at Omaha, Omaha, NE 68182, USA.
出版信息
Int J Mol Sci. 2019 Sep 19;20(18):4654. doi: 10.3390/ijms20184654.
The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) is an immune checkpoint (ICP) overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. To determine important residues for ligand binding, we applied molecular docking studies to PD-1/PD-L1 complex inhibitors against the PD-L1 protein. Our data revealed that the residues Tyr56, Asp122, and Lys124 play critical roles in ligand binding to the PD-L1 protein and they could be used to design ligands that are active against the PD-1/PD-L1 complex. The formation of H-bonds with Arg125 of the PD-L1 protein may enhance the potency of the PD-1/PD-L1 binding.
程序性细胞死亡蛋白 1（PD-1）/程序性细胞死亡配体 1（PD-L1）是在各种类型的肿瘤中过度表达的免疫检查点（ICP），因此，它被认为是癌症治疗的一个重要靶点。为了确定配体结合的重要残基，我们应用分子对接研究来研究 PD-1/PD-L1 复合物抑制剂对 PD-L1 蛋白的作用。我们的数据表明，残基 Tyr56、Asp122 和 Lys124 在配体与 PD-L1 蛋白的结合中起关键作用，它们可用于设计针对 PD-1/PD-L1 复合物的有效配体。与 PD-L1 蛋白的 Arg125 形成氢键可能会增强 PD-1/PD-L1 结合的效力。
Zotero 插件