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

2019 ◽  
Vol 20 (10) ◽  
pp. 2568 ◽  
Author(s):  
Bing Yang ◽  
Shu-Jian Lin ◽  
Jia-Yi Ren ◽  
Tong Liu ◽  
Yue-Ming Wang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Monoclonal Antibody ◽  
Molecular Docking ◽  
Md Simulation ◽  
Factor H ◽  
Complement Factor H ◽  
Energy Calculation ◽  
Complement Factor ◽  
Alanine Scanning ◽  
Computational Alanine Scanning

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.

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

2018 ◽  
Author(s):  
Bing Yang ◽  
Jiayi Ren ◽  
Tong Liu ◽  
Shujian Lin ◽  
Yueming Wang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Molecular Docking ◽  
Md Simulation ◽  
Factor H ◽  
Energy Calculation ◽  
Complement Factor ◽  
Alanine Scanning ◽  
Computational Alanine Scanning ◽  
Antigen Antibody ◽  
Antibody Interactions

The details of antigen-antibody interactions and the identification of epitopes are critical for the development of monoclonal antibody drugs. Ab42 is a native human-derived anti-CFH monoclonal antibody. In this study, the interaction between antigen pCFH and antibody (Ab42) was theoretically demonstrated by molecular docking and MD simulation, combined with free energy calculation and computational alanine scanning (CAS), and key amino acids and epitopes were identified. Experimental alanine scanning (EAS) was then carried out to verify the results of the calculation, and our results indicated that Ab42 antibody forms hydrogen bonds and interacts hydrophobically with pCFH through the Tyr315, Ser100, Gly33, and Tyr53 residues on its CDR, while the main pCFH epitopes are located at the six sites of Pro441, Ile442, Asp443, Asn444, Ile447, and Thr448. In conclusion, this study has explored the mechanism of antigen-antibody interaction from both theoretical and experimental aspects, and our results have important theoretical significance for the design and development of relevant antibody drugs.

A novel monoclonal antibody specific for the 402His variant of complement factor H enables identification of the Tyr402His polymorphic status in serum samples

2007 ◽  
Vol 44 (16) ◽  
pp. 3951
Author(s):  
Svetlana Hakobyan ◽  
Claire L. Harris ◽  
Agustin Tortojada ◽  
Elena Giocochea de Jorge ◽  
Santiago Rodriguez de Cordoba ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Factor H ◽  
Complement Factor H ◽  
Complement Factor ◽  
Serum Samples

Design of potential IKK-β inhibitors using molecular docking and molecular dynamics techniques for their anti-cancer potential

2020 ◽  
Vol 16 ◽  
Author(s):  
Salam Pradeep Singh ◽  
Iftikar Hussain ◽  
Bolin Kumar Konwar ◽  
Ramesh Chandra Deka ◽  
Chingakham Brajakishor Singh
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Md Simulation ◽  
Inflammatory Diseases ◽  
Binding Free Energy ◽  
Anti Cancer ◽  
Dietary Phytochemicals ◽  
Toxicity Analysis ◽  
The Stability ◽  
Stable Trajectory

Aim and Objective: To evaluate a set of seventy phytochemicals for their potential ability to bind the inhibitor of nuclear factor kappaB kinase beta (IKK-β) which is a prime target for cancer and inflammatory diseases. Materials and Methods: Seventy phytochemicals were screened against IKK-β enzyme using DFT-based molecular docking technique and the top docking hits were carried forward for molecular dynamics (MD) simulation protocols. The adme-toxicity analysis was also carried out for the top docking hits. Results: Sesamin, matairesinol and resveratrol were found to be the top docking hits with a total score of -413 kJ/mol, -398.11 kJ/mol and 266.73 kJ/mol respectively. Glu100 and Gly102 were found to be the most common interacting residues. The result from MD simulation observed a stable trajectory with a binding free energy of -107.62 kJ/mol for matairesinol, -120.37 kJ/mol for sesamin and -40.56 kJ/mol for resveratrol. The DFT calculation revealed the stability of the compounds. The ADME-Toxicity prediction observed that these compounds fall within the permissible area of Boiled-Egg and it does not violate any rule for pharmacological criteria, drug-likeness etc. Conclusion: The study interprets that dietary phytochemicals are potent inhibitors of IKK-β enzyme with favourable binding affinity and less toxic effects. In fact, there is a gradual rise in the use of plant-derived molecules because of its lesser side effects compared to chemotherapy. The study has also provided an insight by which the phytochemicals inhibited the IKK-β enzyme. The investigation would also provide in understanding the inhibitory mode of certain dietary phytochemicals in treating cancer.

Complement factor H R1210C among Japanese patients with age-related macular degeneration

2015 ◽  
Vol 59 (5) ◽  
pp. 273-278 ◽  
Author(s):  
Masahiro Miyake ◽  
Masaaki Saito ◽  
Kenji Yamashiro ◽  
Tetsuju Sekiryu ◽  
Nagahisa Yoshimura
Keyword(s):  
Macular Degeneration ◽  
Japanese Patients ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor H ◽  
Complement Factor ◽  
Age Related
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