title: Affinity of HIV-1 antibody 2G12 with monosaccharides: a theoretical study based on explicit and implicit water models.
abstract: In order to develop potential ligands to HIV-1 antibody 2G12 toward HIV-1 vaccine, binding mechanisms of the antibody 2G12 with the glycan ligand of D-mannose and D-fructose were theoretically examined. D-Fructose, whose molecular structure is slightly different from D-mannose, has experimentally shown to have stronger binding affinity to the antibody than that of D-mannose. To clarify the nature of D-fructose's higher binding affinity over D-mannose, we studied interaction between the monosaccharides and the antibody using ab initio fragment molecular orbital (FMO) method considering solvation effect as implicit model (FMO-PCM) as well as explicit water model. The calculated binding free energies of the glycans were qualitatively well consistent with the experimentally reported order of their affinities with the antibody 2G12. In addition, the FMO-PCM calculation elucidated the advantages of D-fructose over D-mannose in the solvation energy as well as the entropic contribution term obtained by MD simulations. The effects of explicit water molecules observed in the X-ray crystal structure were also scrutinized by means of FMO methods. Significant pair interaction energies among D-fructose, amino acids, and water molecules were uncovered, which indicated contributions from the water molecules to the strong binding ability of D-fructose to the antibody 2G12. These FMO calculation results of explicit water model as well as implicit water model indicated that the strong binding of D-fructose over D-mannose was due to the solvation effects on the D-fructose interaction energy.
authors.affiliation: Department of Chemistry and Biochemistry, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Koyama
authors.affiliation: Center for Natural Sciences, College of Liberal Arts and Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ueno-Noto
authors.affiliation: Department of Chemistry and Biochemistry, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan. Electronic address: takano.keiko@ocha.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Takano
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000915:Antibody Affinity; D000080908:Broadly Neutralizing Antibodies; D018360:Crystallography, X-Ray; D005632:Fructose / Q000737:chemistry / Q000276:immunology; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D008358:Mannose / Q000737:chemistry / Q000276:immunology; D008958:Models, Molecular; D009005:Monosaccharides / Q000737:chemistry / Q000276:immunology*; D011789:Quantum Theory; D012996:Solutions; D014867:Water / Q000737:chemistry*
chemical_list: C529157:2G12 monoclonal antibody; D000911:Antibodies, Monoclonal; D000080908:Broadly Neutralizing Antibodies; D015483:HIV Antibodies; D009005:Monosaccharides; D012996:Solutions; D014867:Water; D005632:Fructose; D008358:Mannose
keywords: Binding free energy; FMO-PCM; HIV-1 antibody 2G12; In silico ligand structure; Solvation effect; d-Mannose and d-fructose