Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia.
J Biomol Struct Dyn. 2024 Jul;42(11):5657-5668. doi: 10.1080/07391102.2023.2227717. Epub 2023 Jun 30.
Immunotherapy using checkpoint inhibitors blocks the checkpoint proteins (programmed cell death receptor-1; PD-1) from binding with their corresponding ligands (programmed cell death receptor ligand-1; PD-L1) to regulate cell signaling pathways. The marine environment holds a huge source of small molecules that are understudied which can be developed as an inhibitor. Hence, this study investigated the inhibitory effect of 19 algae-derived small molecules against PD-L1 by using molecular docking, absorption, distribution, metabolism, and elimination (ADME) properties and molecular dynamics simulations (MDS). The molecular docking revealed that the binding energy of the six best compounds ranges from -11.1 to -9.1 kcal/mol. Fucoxanthinol, in particular, has the strongest binding energy at -11.1 kcal/mol with three hydrogen bonds (ASN:63A, GLN:66A, and ASP:122A). Meanwhile, the MDS demonstrated that the ligands were strongly bound to the protein, indicating the stability of the complexes. In summary, the identified compounds are potential PD-L1 inhibitors in immunotherapy.Communicated by Ramaswamy H. Sarma.
免疫疗法使用检查点抑制剂阻止检查点蛋白（程序性死亡受体-1；PD-1）与其相应的配体（程序性死亡受体配体-1；PD-L1）结合，从而调节细胞信号通路。海洋环境蕴藏着大量未被充分研究的小分子，这些小分子可以被开发成抑制剂。因此，本研究通过分子对接、吸收、分布、代谢和消除（ADME）特性以及分子动力学模拟（MDS），研究了 19 种藻类来源的小分子对 PD-L1 的抑制作用。分子对接结果表明，六种最佳化合物的结合能范围在-11.1 到-9.1 kcal/mol 之间。特别是岩藻黄质醇具有最强的结合能，为-11.1 kcal/mol，与三个氢键（ASN:63A、GLN:66A 和 ASP:122A）结合。同时，MDS 表明配体与蛋白质结合牢固，表明复合物的稳定性。综上所述，鉴定出的化合物是免疫疗法中潜在的 PD-L1 抑制剂。Ramaswamy H. Sarma 通讯。
