Mechanism of Baicalein Inhibiting the PD-1/PD-L1 Interaction Based on Molecular Dynamics Simulation and Experiment Research

被引：0
|
作者：
Yan G.U.O. [1 ]
Yilin G.U.O. [1 ]
Boping L.I.U. [2 ,3 ]
Jianguo X.U. [1 ]
机构：
[1] College of Food Science, Shanxi Normal University, Taiyuan
[2] College of Materials and Energy, South China Agricultural University, Guangzhou
[3] Key Laboratory for Bio-Based Materials and Energy of Ministry of Education, South China Agricultural University, Guangzhou
来源：
Science and Technology of Food Industry | 2024年 / 45卷 / 02期
关键词：
baicalein; inhibition mechanism; molecular dynamics simulation; natural small molecules; PD-/PD-L1;
D O I：
10.13386/j.issn1002-0306.2023090095
中图分类号：
学科分类号：
摘要：
To study the molecular mechanism of baicalein interrupting the programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway, molecular docking, molecular dynamics simulation, binding free energy calculation 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 showed 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 demonstrated 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 79.47 µg/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. © 2024 Chinese Academy of Agriculture Sciences. All rights reserved.
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页码：40 / 47
页数：7
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