title: Improved scFv anti-HIV-1 p17 binding affinity guided from the theoretical calculation of pairwise decomposition energies and computational alanine scanning.
abstract: 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.
authors.affiliation: 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.
authors.forename: Panthip
authors.initials: P
authors.lastname: Tue-ngeun
authors.forename: Kanchanok
authors.initials: K
authors.lastname: Kodchakorn
authors.forename: Piyarat
authors.initials: P
authors.lastname: Nimmanpipug
authors.forename: Narin
authors.initials: N
authors.lastname: Lawan
authors.forename: Sawitree
authors.initials: S
authors.lastname: Nangola
authors.forename: Chatchai
authors.initials: C
authors.lastname: Tayapiwatana
authors.forename: Noorsaadah Abdul
authors.initials: NA
authors.lastname: Rahman
authors.forename: Sharifuddin Md
authors.initials: SM
authors.lastname: Zain
authors.forename: Vannajan Sanghiran
authors.initials: VS
authors.lastname: Lee
mesh_terms: D000915:Antibody Affinity; D015488:HIV Antigens / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D056004:Molecular Dynamics Simulation; D057127:Single-Chain Antibodies / Q000737:chemistry* / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000276:immunology
chemical_list: D015488:HIV Antigens; D057127:Single-Chain Antibodies; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1