title: Proposed atomic structure of a truncated human immunodeficiency virus glycoprotein gp120 derived by molecular modeling: target CD4 recognition and docking mechanism.
abstract: The atomic structure of a truncated glycoprotein gp120 from human immunodeficiency virus 1 (HIV-1) that contains the principal neutralizing antigenic sites and the CD4 binding domain has been derived by molecular dynamics and calculation of potential energy using the DREIDING force field. The resultant N-glycosylated molecular model is consistent with known properties of gp120 and docks with CD4 with a substantial reduction in the sum of the internal potential energies of the individual proteins (delta E = -200 kcal/mol). The primary mechanism of recognition and binding is the insertion of the solvent-accessible Phe-43 of CD4 into a gp120 solvent-accessible acceptor pit formed by Trp-427, Tyr-435, and the high-mannose oligosaccharide N-linked to Asn-230. delta E for the nonglycosylated complex is reduced significantly (-75 kcal/mol). Binding is by pi-pi* interactions of the aromatic groups forming a hydrophobic, thermodynamically stable environment for these functional noncovalent bonding participants. This model for gp120 provides a theoretical basis for the evaluation of HIV molecular pathogenesis involving the env proteins, the analysis of conformation on functional immune response of the host, and the design of nonproteinaceous inhibitors specific for the CD4 binding site on gp120.
authors: Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140.
authors: J L
authors: JL
authors: Gabriel
authors: W M
authors: WM
authors: Mitchell
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D002151:Calorimetry; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004220:Disulfides / Q000032:analysis; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D015704:CD4 Antigens; D004220:Disulfides; D015699:HIV Envelope Protein gp120; D009844:Oligosaccharides