title: Computer-aided molecular modeling of the binding site architecture for eight monoclonal antibodies that bind a high potency guanidinium sweetener.
abstract: Computer-aided molecular modeling of the antibody binding site of eight different monoclonal antibodies (mAb) that bind the intense sweetener ligand (N-(p-cyanophenyl)-N'-diphenylmethyl) guanidine acetic acid was completed using canonical loop structures and framework regions from known immunoglobulins as "parent structures" for the molecular scaffoldings. The models of the fragment variable (Fv) region of the mAb were analyzed for the presence and location of residues predicted to be involved in ligand binding. Several binding site tryptophan residues in these models were located in positions that support previous flurospectroscopic observations of the mAb-ligand complexation. Computer-aided renderings of the electrostatic potential at the van der Waals surface of the Fv region were compared and found to be consistent with the ligand binding specificity profiles for the different mAb. The Fv model of mAb NC6.8 was consistent with the binding site features determined in the Fab structure recently solved by X-ray diffraction techniques. These Fv models should provide an adequate basis for site-directed mutagenesis experiments in order to characterize interactive motifs in the mAb binding site.
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station 77843.
authors.forename: J M
authors.initials: JM
authors.lastname: Anchin
authors.forename: C
authors.initials: C
authors.lastname: Mandal
authors.forename: C
authors.initials: C
authors.lastname: Culberson
authors.forename: S
authors.initials: S
authors.lastname: Subramaniam
authors.forename: D S
authors.initials: DS
authors.lastname: Linthicum
mesh_terms: D000085:Acetates / Q000276:immunology* / Q000378:metabolism; D000465:Algorithms; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D001666:Binding Sites, Antibody; D017076:Computer-Aided Design; D015195:Drug Design; D006146:Guanidines / Q000276:immunology* / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D012984:Software; D013549:Sweetening Agents / Q000378:metabolism*
chemical_list: D000085:Acetates; D000911:Antibodies, Monoclonal; D006146:Guanidines; D007135:Immunoglobulin Variable Region; D013549:Sweetening Agents; C083643:NC 174