Abstract
Blocking the programmed death receptor 1 (PD-1)/programmed death ligand 1 protein (PD-L1) interaction has come up as a promising cancer immunotherapy. Pembrolizumab is a therapeutic monoclonal antibody targeting PD-1 and received widespread attention. However, the messages for the paratope and epitope residues of pembrolizumab are insufficient. Here molecular dynamics (MD) simulation was used to map epitope on PD-1 to paratope residues on pembrolizumab. A total of twenty-nine key residues were predicted in the PD-1/pembrolizumab interaction. Of the fourteen epitope residues, three (i.e., ASN66, LYS78 and ALA132 on PD-1) were found to play critical roles in the interaction of PD-1 and PD-L1. Therefore, pembrolizumab prevents PD-L1 from interacting with PD-1 through steric hindrance, and the key residues sorted out here were potential hotspots for the optimization of pembrolizumab.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (Grant No. 31500591) and the Natural Science Foundation of Guangdong Province (Grant No. 2015A030310106). All simulations were supported by the National Super Computer Center in Guangzhou.
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Liu, W., Liu, G. (2017). Mapping Paratope and Epitope Residues of Antibody Pembrolizumab via Molecular Dynamics Simulation. In: Cai, Z., Daescu, O., Li, M. (eds) Bioinformatics Research and Applications. ISBRA 2017. Lecture Notes in Computer Science(), vol 10330. Springer, Cham. https://doi.org/10.1007/978-3-319-59575-7_11
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