Wenping Liu
ABSTRACT
Cancer is a major cause of morbidity and mortality worldwide and constitutes a considerable burden on society. The inhibitors targeting the programmed death receptor–1 (PD-1)/programmed death ligand 1 protein (PD-L1) pathway are the most promising approaches for cancer treatment. Toripalimab, a humanized IgG4 antibody targeting PD-1, was approved by the China National Medical Products Administration in 2018. Although the crystal structure of the toripalimab/PD-1 complex was reported in 2019, it was just a frozen structure and needs to be further studied dynamically to fully understand the blockade mechanism of the antibody toripalimab. Thus, long-time molecular dynamics (MD) simulations were performed for toripalimab/PD-1 and PD-1/PD-L1 complexes. Nine residues were predicted to be epitope and paratope residues for toripalimab, including PD-1PRO130, PD-1LYS131, PD-1ALA132, PD-1ILE134 and GLU99H, GLY100H, THR102H, TYR111H, HSE31L. The PD-1ALA132 locating on the FG loop is the common binding site for PD-L1 and toripalimab. Thus, antibody toripalimab block PD-1/PD-L1 interaction through direct competitive binding of the FG loop of PD-1.
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