Molecular Docking and Molecular Dynamics (MD) Simulation of Human Anti-Complement Factor H (CFH) Antibody Ab42 and CFH Polypeptide.

Bing Yang, Shu-Jian Lin, Jia-Yi Ren, Tong Liu, Yue-Ming Wang, Cheng-Ming Li, Wen-Wen Xu, You-Wen He, Wei-Hong Zheng, Jian Zhao, Xiao-Hui Yuan, Hua-Xin Liao

Journal: International journal of molecular sciences 2019;20(10):2568

PMID: 31130605

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Abstract

An understanding of the interaction between the antibody and its targeted antigen and knowing of the epitopes are critical for the development of monoclonal antibody drugs. Complement factor H (CFH) is implied to play a role in tumor growth and metastasis. An autoantibody to CHF is associated with anti-tumor cell activity. The interaction of a human monoclonal antibody Ab42 that was isolated from a cancer patient with CFH polypeptide (pCFH) antigen was analyzed by molecular docking, molecular dynamics (MD) simulation, free energy calculation, and computational alanine scanning (CAS). Experimental alanine scanning (EAS) was then carried out to verify the results of the theoretical calculation. Our results demonstrated that the Ab42 antibody interacts with pCFH by hydrogen bonds through the Tyr315, Ser100, Gly33, and Tyr53 residues on the complementarity-determining regions (CDRs), respectively, with the amino acid residues of Pro441, Ile442, Asp443, Asn444, Ile447, and Thr448 on the pCFH antigen. In conclusion, this study has explored the mechanism of interaction between Ab42 antibody and its targeted antigen by both theoretical and experimental analysis. Our results have important theoretical significance for the design and development of relevant antibody drugs.

Address: Institute of Biomedicine, Jinan University, Guangzhou 510632, China. [email protected].; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China. [email protected].; Institute of Biomedicine, Jinan University, Guangzhou 510632, China. [email protected].; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China. [email protected].; Zhuhai College of Jilin University, Zhuhai 519041, China. [email protected].; Institute of Biomedicine, Jinan University, Guangzhou 510632, China. [email protected].; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China. [email protected].; Institute of Biomedicine, Jinan University, Guangzhou 510632, China. [email protected].; National Engineering Research Center of Genetic Medicine, Guangzhou 510632, China. [email protected].; Institute of Biomedicine, Jinan University, Guangzhou 510632, China. [email protected].; National Engineering Research Center of Genetic Medicine, Guangzhou 510632, China. [email protected].; Institute of Biomedicine, Jinan University, Guangzhou 510632, China. [email protected].; National Engineering Research Center of Genetic Medicine, Guangzhou 510632, China. [email protected].; Department of Immunology, Duke University Medical Center, Durham, NC 27503, USA. [email protected].; Zhuhai Trinomab Biotechnology Co., Ltd., Zhuhai 519040, China. [email protected].; Zhuhai Trinomab Biotechnology Co., Ltd., Zhuhai 519040, China. [email protected].; Institute of Biomedicine, Jinan University, Guangzhou 510632, China. [email protected].; Zhuhai Trinomab Biotechnology Co., Ltd., Zhuhai 519040, China. [email protected].; Institute of Biomedicine, Jinan University, Guangzhou 510632, China. [email protected].; Zhuhai Trinomab Biotechnology Co., Ltd., Zhuhai 519040, China. [email protected].

DOI: 10.3390/ijms20102568

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https://assays.cancer.gov/non-CPTAC-2658

MeSH Terms: Antibodies, Monoclonal, Antigen-Antibody Reactions, Autoantibodies, Complement Factor H, Complementarity Determining Regions, Epitopes, Humans, Molecular Docking Simulation, Molecular Dynamics Simulation, Neoplasms, Peptides, Protein Conformation