Molecular Mechanism of Small-Molecule Inhibitors in Blocking the PD-1/PD-L1 Pathway through PD-L1 Dimerization.

ABSTRACT: Programmed cell death-1 (PD-1), which is a molecule involved in the inhibitory signal in the immune system and is important due to blocking of the interactions between PD-1 and programmed cell death ligand-1 (PD-L1), has emerged as a promising immunotherapy for treating cancer. In this work, molecular dynamics simulations were performed on complex systems consisting of the PD-L1 dimer with (S)-BMS-200, (R)-BMS-200 and (MOD)-BMS-200 (i.e., S, R and MOD systems) to systematically evaluate the inhibitory mechanism of BMS-200-related small-molecule inhibitors in detail. Among them, (MOD)-BMS-200 was modified from the original (S)-BMS-200 by replacing the hydroxyl group with a carbonyl to remove its chirality. Binding free energy analysis indicates that BMS-200-related inhibitors can promote th

SUBMITTER: Guo Y 

PROVIDER: S-EPMC8125578 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature