title: Pairwise decomposition of residue interaction energies of single chain Fv with HIV-1 p17 epitope variants.
abstract: Computational assisted modeling was carried out to investigate the importance of specific residues in the binding site of scFv. In this study, scFv against HIV-1 epitope at the C-terminal on p17 (scFv anti-p17) was used as a candidate molecule for evaluating the method. The wild-type p17 and its nine natural mutants were docked with scFv anti-p17. Potential mean force (PMF) scores predicted the most favorable binding interaction, and the correlation agreed well with the corresponding activity data from the peptide based ELISA. In the interaction with solvent molecules, the 3D structures of scFv anti-p17 and selected peptide epitopes were further investigated by molecular dynamics (MDs) simulation with the AMBER 9 program. Post-processing of the snapshot at equilibrium was performed to evaluate the binding free energy and pairwise decomposition or residue-based energy calculation of complexes in solution using the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) protocol. Our results demonstrated that the specific residues located in the complementary determining regions (CDRs) of scFv anti-p17, MET100, LYS101, ASN169, HIS228, and LEU229, play a crucial role in the effective binding interaction with the absolute relative decomposed energy more than 2.00 kcal/mol in comparison to the original substrate.
authors.affiliation: Computational Simulation and Modeling Laboratory (CSML), Department of Chemistry and Center for Innovation in Chemistry, Chiang Mai University, Chiang Mai, 50200, Thailand. vannajan@gmail.com
authors.forename: Vannajan Sanghiran
authors.initials: VS
authors.lastname: Lee
authors.forename: Panthip
authors.initials: P
authors.lastname: Tue-ngeun
authors.forename: Sawitree
authors.initials: S
authors.lastname: Nangola
authors.forename: Kuntida
authors.initials: K
authors.lastname: Kitidee
authors.forename: Jitrayut
authors.initials: J
authors.lastname: Jitonnom
authors.forename: Piyarat
authors.initials: P
authors.lastname: Nimmanpipug
authors.forename: Supat
authors.initials: S
authors.lastname: Jiranusornkul
authors.forename: Chatchai
authors.initials: C
authors.lastname: Tayapiwatana
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000914:Antibodies, Viral / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D015488:HIV Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D020836:Protein Structure, Quaternary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D057127:Single-Chain Antibodies / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D015488:HIV Antigens; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1