WCSE

An In-silico Study: Investigating the Blockade Mechanism of Therapeutic Antibody Durvalumab

Abstract— Durvalumab, approved by the US Food and Drug Administration (FDA) in 2017, is a human monoclonal antibody targeting the programmed death receptor 1 (PD-1)/ programmed death ligand 1 (PD-L1) pathway. Although the crystal structure of the durvalumab/PD-L1 complex is reported in 2017, some key residues might be missed in that static structure. Here, molecular dynamics simulation (MD) was used to investigate the blockade mechanism of antibody durvalumab dynamically. Our results showed that the interfacial residues of PD-L1 upon durvalumab binding locate on the C strand (PD-L1GLU58), CC’ loop (PD-L1GLU60), F strand (PD-L1ARG113) and G strand (PD-L1ARG125). The overlap binding region on PD-L1 for PD-1 and durvalumab is the G strand. Thus, antibody durvalumab block PD-1/PD-L1 interaction through competitive binding of the G strand of PD-L1.

Index Terms— durvalumab, blockade mechanism, molecular dynamics simulation

Wenping Liu
Institute of Medical Devices, Guangdong Food and Drug Vocational College, CHINA
Ting Chen
Institute of Medical Devices, Guangdong Food and Drug Vocational College, CHINA
Guangjian Liu
Clinical Data Center, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, CHINA
Haoyu Jin
Institute of Medical Devices, Guangdong Food and Drug Vocational College, CHINA

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Cite: Wenping Liu, Ting Chen, Guangjian Liu, Haoyu Jin, "An In-silico Study: Investigating the Blockade Mechanism of Therapeutic Antibody Durvalumab ," 2021 The 11th International Workshop on Computer Science and Engineering (WCSE 2021), pp. 128-132, Shanghai, China, June 19-21, 2021.