Structural Insights of PD-1/PD-L1 Axis: An In silico Approach.

IF 1.9 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current protein & peptide science Pub Date : 2024-01-01 DOI:10.2174/0113892037297012240408063250

Shishir Rohit, Mehul Patel, Yogesh Jagtap, Umang Shah, Ashish Patel, Swayamprakash Patel, Nilay Solanki

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引用次数: 0

Abstract

Background: Interaction of PD-1 protein (present on immune T-cell) with its ligand PD-L1 (over-expressed on cancerous cell) makes the cancerous cell survive and thrive. The association of PD-1/PD-L1 represents a classical protein-protein interaction (PPI), where receptor and ligand binding through a large flat surface. Blocking the PD-1/PDL-1 complex formation can restore the normal immune mechanism, thereby destroying cancerous cells. However, the PD-1/PDL1 interactions are only partially characterized.

Objective: We aim to comprehend the time-dependent behavior of PD-1 upon its binding with PD-L1.

Methods: The current work focuses on a molecular dynamics simulation (MDs) simulation study of apo and ligand bound PD-1.

Results: Our simulation reveals the flexible nature of the PD-1, both in apo and bound form. Moreover, the current study also differentiates the type of strong and weak interactions which could be targeted to overcome the complex formation.

Conclusion: The current article could provide a valuable structural insight about the target protein (PD-1) and its ligand (PD-L1) which could open new opportunities in developing small molecule inhibitors (SMIs) targeting either PD-1 or PD-L1.

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PD-1/PD-L1 轴的结构洞察：一种硅学方法。

背景：PD-1蛋白（存在于免疫T细胞上）与其配体PD-L1（在癌细胞上过度表达）的相互作用使癌细胞得以生存和生长。PD-1/PD-L1 的结合是经典的蛋白质-蛋白质相互作用（PPI），即受体和配体通过一个大的平面结合。阻断 PD-1/PDL-1 复合物的形成可以恢复正常的免疫机制，从而消灭癌细胞。然而，PD-1/PDL1 的相互作用只有部分表征：我们旨在理解 PD-1 与 PD-L1 结合后随时间变化的行为：当前工作的重点是分子动力学模拟（MDs）仿真研究与配体结合的PD-1：结果：我们的模拟揭示了 PD-1 的灵活特性，无论是其疏体形式还是与配体结合的形式。此外，目前的研究还区分了强相互作用和弱相互作用的类型，可以有针对性地克服复合物的形成：结论：本文提供了关于靶蛋白（PD-1）及其配体（PD-L1）的有价值的结构见解，这将为开发针对 PD-1 或 PD-L1 的小分子抑制剂（SMIs）带来新的机遇。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current protein & peptide science 生物-生化与分子生物学

CiteScore

5.20

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Current Protein & Peptide Science publishes full-length/mini review articles on specific aspects involving proteins, peptides, and interactions between the enzymes, the binding interactions of hormones and their receptors; the properties of transcription factors and other molecules that regulate gene expression; the reactions leading to the immune response; the process of signal transduction; the structure and function of proteins involved in the cytoskeleton and molecular motors; the properties of membrane channels and transporters; and the generation and storage of metabolic energy. In addition, reviews of experimental studies of protein folding and design are given special emphasis. Manuscripts submitted to Current Protein and Peptide Science should cover a field by discussing research from the leading laboratories in a field and should pose questions for future studies. Original papers, research articles and letter articles/short communications are not considered for publication in Current Protein & Peptide Science.