Computational analysis of PD-L1 dimerization mechanism induced by small molecules and potential dynamical properties

Xu, Xiaole; Luo, Song; Zhao, Xiaoyu; Tang, Bolin; Zhang, Enhao; Liu, Jinxin; Duan, Lili

doi:10.1016/j.ijbiomac.2024.130921

Cited by 3 publications

(1 citation statement)

References 75 publications

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“…Combining free energy can be used to quantitatively and rapidly evaluate the molecular recognition ability between receptors and ligands, and can characterize the strength of binding abilities. [38] As shown in Table 4, the main source of the binding affinity between inhibitors and proteins in the system is van der Waals interaction energy, and electrostatic interaction energy.…”

Section: Analysis Of Molecular Dynamics Simulationsmentioning

confidence: 99%

Design of Biphenyl‐Type Programmed Cell Death‐Ligand 1 Inhibitors Using 3D‐QSAR, Molecular Docking, and Molecular Dynamics Simulation

Zhu,

Xu,

et al. 2024

ChemistrySelect

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Blocking the interaction between programmed cell death‐1 (PD‐1) and programmed cell death‐ligand 1 (PD‐L1) is a crucial immunotherapeutic strategy for cancer. Currently, all inhibitors available on the market that target PD‐1/PD‐L1 are monoclonal antibodies, with no small molecule drugs yet accessible. This study focused on PD‐L1 and conducted three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) research on 39 PD‐L1 inhibitors using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The CoMFA (q2=0.593, r2=0.991) and CoMSIA (q2=0.542, r2=0.971) models were successfully established. Based on these models, a series of structurally novel and potentially active PD‐L1 inhibitors (37 a–37 e) were designed. Among these compounds, 37 c exhibited superior performance, with CoMFA predicting a pIC50 value of 9.204 and CoMSIA predicting a pIC50 value of 8.597. Further molecular docking and molecular dynamics simulations revealed that compound 37 c establishes hydrophobic interactions with BTyr56 and BVal68 of PD‐L1, engages in hydrogen bonds with AAsp122, ALys124, and BTyr123, and forms electrostatic interactions with ALys124 and AMet115. The design of this biphenyl series of inhibitors offers additional options for the development of small molecule inhibitors targeting PD‐L1, with 37 c expected to be a promising inhibitor of PD‐L1.

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Section: Analysis Of Molecular Dynamics Simulationsmentioning

confidence: 99%

Design of Biphenyl‐Type Programmed Cell Death‐Ligand 1 Inhibitors Using 3D‐QSAR, Molecular Docking, and Molecular Dynamics Simulation

Zhu,

Xu,

et al. 2024

ChemistrySelect

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Molecular insight into binding affinities and blockade effects of selected flavonoid compounds on the PD-1/PD-L1 pathway

Guo,

Tong,

Liang

et al. 2024

RSC Adv.

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Effective control of postoperative recurrence of pregnancy-related gastric cancer using anti-PD-1 as a monotherapy: a case report

Liu,

Li,

Zhu

et al. 2024

Front. Oncol.

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Pregnancy-related gastric cancer is characterized by a refractory nature and poor prognosis; few gastric cancer cases during pregnancy achieved acceptable outcomes by using anti-PD-1 as a monotherapy. A 32-year-old pregnant female patient was admitted to the emergency department of the obstetrics and gynecology department and eventually diagnosed with gastric cancer. Radical surgery for gastric cancer was conducted after the termination of pregnancy. At 1-year postoperative follow-up, tumor recurrence was revealed. This patient has achieved a decrease in tumor burden after receiving anti-PD-1 as a monotherapy. This case documents tumor response to PD-1 monotherapy in pregnancy-related gastric cancer and highlights the potential for future use in specific clinical scenarios.

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Computational analysis of PD-L1 dimerization mechanism induced by small molecules and potential dynamical properties

Cited by 3 publications

References 75 publications

Design of Biphenyl‐Type Programmed Cell Death‐Ligand 1 Inhibitors Using 3D‐QSAR, Molecular Docking, and Molecular Dynamics Simulation

Design of Biphenyl‐Type Programmed Cell Death‐Ligand 1 Inhibitors Using 3D‐QSAR, Molecular Docking, and Molecular Dynamics Simulation

Molecular insight into binding affinities and blockade effects of selected flavonoid compounds on the PD-1/PD-L1 pathway

Effective control of postoperative recurrence of pregnancy-related gastric cancer using anti-PD-1 as a monotherapy: a case report

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