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

GUO Yan; GUO Yilin; LIU Boping; XU Jianguo

doi:10.13386/j.issn1002-0306.2023090095

Volume 45 Issue 2

Jan. 2024

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Science and Technology of Food Industry > 2024 > 45(2): 40-47. > DOI: 10.13386/j.issn1002-0306.2023090095

GUO Yan, GUO Yilin, LIU Boping, et al. Mechanism of Baicalein Inhibiting the PD-1/PD-L1 Interaction Based on Molecular Dynamics Simulation and Experiment Research[J]. Science and Technology of Food Industry, 2024, 45(2): 40−47. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023090095.

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

GUO Yan^1,,
GUO Yilin¹,
LIU Boping^{2, 3, ,},
XU Jianguo^1, ,

1.
College of Food Science, Shanxi Normal University, Taiyuan 030031, China
2.
College of Materials and Energy, South China Agricultural University, Guangzhou 510630, China
3.
Key Laboratory for Bio-Based Materials and Energy of Ministry of Education,South China Agricultural University, Guangzhou 510630, China

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Received Date: September 10, 2023
Available Online: November 12, 2023

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Abstract

Abstract

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.
- PD-/PD-L1,
- natural small molecules,
- baicalein,
- molecular dynamics simulation,
- inhibition mechanism

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References

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

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