期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/ijms20102568
关键词
complement factor H (CFH); molecular docking; molecular dynamics (MD) simulation; computational alanine scanning (CAS); experimental alanine scanning (EAS); complementarity-determining region (CDR)
资金
- Guangdong Innovative and Entrepreneurial Research Team Program [2013Y113]
- Zhuhai Innovative and Entrepreneurial Research Team Program [ZH01110405160015PWC]
- National Basic Research Program of China (973 Program) [2015CB553706]
- Operating Fund of Guangdong Provincial Key Laboratory of Bioengineering Medicine [2014B030301050]
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.
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