Mapping Paratope and Epitope Residues of Antibody Pembrolizumab via Molecular Dynamics Simulation

• Published in: Bioinformatics Research and Applications Vol. 10330; pp. 120 - 127
• Main Authors: Liu, Wenping, Liu, Guangjian
• Format: Book Chapter
• Language: English
• Published: Switzerland Springer International Publishing AG 01.01.2017; Springer International Publishing
• Series: Lecture Notes in Computer Science
• Subjects: Epitope; Molecular dynamics simulation; Paratope; PD-1; PD-L1; Pembrolizumab
• ISBN: 3319595741; 9783319595740
• ISSN: 0302-9743; 1611-3349
• DOI: 10.1007/978-3-319-59575-7_11

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.