Investigating effects of bridging water on the binding of neuraminidase−ligands using computational alanine scanning combined with interaction entropy method

2021 ◽  
pp. 116214
Author(s):  
Yuxi Lv ◽  
Song Luo ◽  
Kaifang Huang ◽  
Han Wang ◽  
Shuheng Dong ◽  
...  
Keyword(s):  
Entropy Method ◽  
Alanine Scanning ◽  
Computational Alanine Scanning

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.

Study of SHMT2 Inhibitors and Their Binding Mechanism by Computational Alanine Scanning

2019 ◽  
Vol 59 (9) ◽  
pp. 3871-3878 ◽  
Author(s):  
Liping He ◽  
Jingxiao Bao ◽  
Yunpeng Yang ◽  
Suzhen Dong ◽  
Lujia Zhang ◽  
...  
Keyword(s):  
Binding Mechanism ◽  
Alanine Scanning ◽  
Computational Alanine Scanning

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.

scholarly journals Improved scFv Anti-HIV-1 p17 Binding Affinity Guided from the Theoretical Calculation of Pairwise Decomposition Energies and Computational Alanine Scanning

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Panthip Tue-ngeun ◽  
Kanchanok Kodchakorn ◽  
Piyarat Nimmanpipug ◽  
Narin Lawan ◽  
Sawitree Nangola ◽  
...  
Keyword(s):  
Interaction Energy ◽  
Binding Affinity ◽  
Theoretical Calculations ◽  
Single Mutation ◽  
Single Chain ◽  
Alanine Scanning ◽  
Single Chain Fv ◽  
Residue Interaction ◽  
Computational Alanine Scanning ◽  
Hiv 1

Computational approaches have been used to evaluate and define important residues for protein-protein interactions, especially antigen-antibody complexes. In our previous study, pairwise decomposition of residue interaction energies of single chain Fv with HIV-1 p17 epitope variants has indicated the key specific residues in the complementary determining regions (CDRs) of scFv anti-p17. In this present investigation in order to determine whether a specific side chain group of residue in CDRs plays an important role in bioactivity, computational alanine scanning has been applied. Molecular dynamics simulations were done with several complexes of original scFv anti-p17 and scFv anti-p17mutants with HIV-1 p17 epitope variants with a production run up to 10 ns. With the combination of pairwise decomposition residue interaction and alanine scanning calculations, the point mutation has been initially selected at the position MET100 to improve the residue binding affinity. The calculated docking interaction energy between a single mutation from methionine to either arginine or glycine has shown the improved binding affinity, contributed from the electrostatic interaction with the negative favorably interaction energy, compared to the wild type. Theoretical calculations agreed well with the results from the peptide ELISA results.

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