摘要
目的研究PD-1/PD-L1小分子免疫抑制剂的作用机制。方法基于PD-1/PD-L1小分子免疫抑制剂的结构,分析受体-配体作用方式,构建药效团模型,并开展分子动力学模拟。结果与结论PD-1/PD-L1靶点活性位点的关键氨基酸包含ILE54、TYR56、MET115和ALA121,活性化合物的结构应包含整点中心、氢键受体和疏水基团。这些药效团特征可用于发现新结构类型的PD-1/PD-L1免疫抑制剂。
To study the mechanism of PD-1/PD-L1 immune checkpoint inhibitors.Based on the structure of PD1/PD-L1,the protein-ligand interaction was analyzed for constructing pharmacophore model,which was verified through molecular dynamics simulation.ILE54,TYR56,MET115 and ALA121 are crucial residues within PD1/PDL1 pocket,participating in molecular interaction with PD-1/PD-L1 inhibitors.Chemical features including positive charged nitrogen atom,hydrogen bond acceptor as well as hydrophobic spheres are essential for PD-1/PD-L1 immune checkpoint inhibitors.These results will be helpful for discovery of novel PD-1/PD-L1 immune checkpoint inhibitors.
作者
张逸腾
刘欣悦
王健
程卯生
ZHANG Yi⁃teng;LIU Xin⁃yue;WANG Jian;CHENG Mao⁃sheng(School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China;Key Laboratory of Structure⁃Based Drug Design and Discovery,Ministry of Education,Shenyang Pharmaceutical University,Shenyang 110016,China;School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)
出处
《中国药物化学杂志》
CAS
CSCD
北大核心
2020年第4期209-216,共8页
Chinese Journal of Medicinal Chemistry
基金
辽宁省大学生创新创业项目(201910163204)
