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

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 th...

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Published in:BioMed Research International Vol. 2013; pp. 713585 - 713586
Main Authors: Tue-Ngeun, Panthip, Kodchakorn, Kanchanok, Nimmanpipug, Piyarat, Lawan, Narin, Nangola, Sawitree, Tayapiwatana, Chatchai, Rahman, Noorsaadah Abdul, Zain, Sharifuddin Md, Lee, Vannajan Sanghiran
Format: Journal Article
Published: Wiley-Blackwell 2013
Online Access:View this record in EBSCOhost
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        atl: Improved scFv Anti-HIV-1 p17 Binding Affinity Guided from the Theoretical Calculation of Pairwise Decomposition Energies and Computational Alanine Scanning.
      aug:
        au:
          Tue-Ngeun, Panthip
          Kodchakorn, Kanchanok
          Nimmanpipug, Piyarat
          Lawan, Narin
          Nangola, Sawitree
          Tayapiwatana, Chatchai
          Rahman, Noorsaadah Abdul
          Zain, Sharifuddin Md
          Lee, Vannajan Sanghiran
        affil: Computational Simulation Modelling Laboratory (CSML), Department of Chemistry and Center of Excellence for Innovation in Chemistry and Materials Science Research Center, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand.
      sug:
        subj:
          Antigen-Antibody Reactions
          Antigens, Viral
          Computer Simulation
          Immunoglobulins, Fab
          Proteins
          Antigens, Viral Immunology
          Immunoglobulins, Fab Immunology
          Proteins Immunology
      ab: 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 antip17. 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.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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