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

被引：35

作者：

Yang, Bing ^{[1
,2
]}

Lin, Shu-Jian ^{[1
,2
]}

Ren, Jia-Yi ^{[3
]}

Liu, Tong ^{[1
,2
]}

Wang, Yue-Ming ^{[1
,4
]}

Li, Cheng-Ming ^{[1
,4
]}

Xu, Wen-Wen ^{[1
,4
]}

He, You-Wen ^{[5
]}

Zheng, Wei-Hong ^{[6
]}

Zhao, Jian ^{[6
]}

Yuan, Xiao-Hui ^{[1
,6
]}

Liao, Hua-Xin ^{[1
,6
]}

机构：

[1] Jinan Univ, Inst Biomed, Guangzhou 510632, Guangdong, Peoples R China

[2] Guangdong Prov Key Lab Bioengn Med, Guangzhou 510632, Guangdong, Peoples R China

[3] Jilin Univ, Zhuhai Coll, Zhuhai 519041, Peoples R China

[4] Natl Engn Res Ctr Genet Med, Guangzhou 510632, Guangdong, Peoples R China

[5] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27503 USA

[6] Zhuhai Trinomab Biotechnol Co Ltd, Zhuhai 519040, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 10期

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); ALANINE SCANNING MUTAGENESIS; MM-PBSA; PROTEIN DOCKING; PERFORMANCE; VALIDATION; GROMACS; CANCER; ZRANK;

D O I：

10.3390/ijms20102568

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：14

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