Wenping Liu
ABSTRACT
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. BMS-936559 is a fully human IgG4 antibody blocking PD-L1. Although the crystal structure of the BMS-936559/PD-L1 complex was reported in 2016, providing us the complex interface at atom level, it was just a frozen structure and some key interaction residues might be missed. Thus, molecular dynamics (MD) simulation is used to map the epitope to paratope residues for BMS-936559 dynamically. Two residues, including PD-L1ASP49 on PD-L1 and TYR32L on the light chain of BMS-936559, were newly sorted out in simulations and there are altogether eight residues predicted critical in the complex interface, including PD-L1ASP49, PD-L1TYR56, PD-L1GLU58, PD-L1HIS69 on PD-L1, and LYS57H, HIS59H, SER106H, TYR32L on both heavy and light chains of BMS-936559.
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