食品工业科技2024，Vol.45Issue(2)：40-47,8.DOI:10.13386/j.issn1002-0306.2023090095
基于分子动力学模拟与实验验证探讨黄芩素抑制PD-1/PD-L1相互作用的分子机制
Mechanism of Baicalein Inhibiting the PD-1/PD-L1 Interaction Based on Molecular Dynamics Simulation and Experiment Research
摘要
Abstract
To study the molecular mechanism of baicalein interrupting the programmed cell death-1(PD-1)and progra-mmed cell death-ligand 1(PD-L1)pathway,molecular docking,molecular dynamics simulation,binding free energy calcu-lation and principal component analysis were first performed to predict the inhibition effect of baicalein on this pathway,which was verified by enzyme-linked immunosorbent assay(ELISA)subsequently.Binding free energy calculations show-ed that the affinity of baicalein to the PD-L1 dimer was-32.41±0.31 kcal/mol.Free energy decomposition,contact numbers and nonbonded interaction results revealed that baicalein mainly interacted with the C-,C'-,F-and G-sheet domains of the PD-L1 dimer.Importantly,nonpolar interactions between the key residues Tyr56,Met115,Ala121,Asp122 and baicalein were dominant factors during the binding process.Cross-correlation matrixes and secondary structure results further demo-nstrated that baicalein could stably interact with the sheet domains of the PD-L1 dimer.The result of ELISA showed that the IC50 value of baicalein for inhibiting the PD-1/PD-L1 interaction was 79.47µg/L.In conclusion,this study revealed that baicalein could directly bind to the PD-L1 dimer,thus blocking the PD-1/PD-L1 interaction,would provide basis for discovering natural small-molecule inhibitors of this pathway.关键词
程序性细胞死亡-1/程序性细胞死亡配体1/天然小分子/黄芩素/分子动力学模拟/抑制机制Key words
PD-/PD-L1/natural small molecules/baicalein/molecular dynamics simulation/inhibition mechanism分类
医药卫生引用本文复制引用
郭妍,郭怡琳,刘柏平,徐建国..基于分子动力学模拟与实验验证探讨黄芩素抑制PD-1/PD-L1相互作用的分子机制[J].食品工业科技,2024,45(2):40-47,8.基金项目
山西省基础研究计划项目(202203021212392) （202203021212392）
山西省高等学校科技创新计划项目(2022L262). （2022L262）
