title: A common pharmacophoric footprint for AIDS vaccine design.
abstract: The most promising target antigen for an HIV vaccine designed using the classic antibody strategy has been the viral coat protein gp120. Unfortunately, its high variability has prevented this approach. We examine here a 15-residue peptide derived from the CD4-binding domain of gp120. By use of molecular dynamics computer simulation, it is shown that despite considerable sequence variation, the three-dimensional structure of the peptide is preserved over the full range of clade-specific sequences. Furthermore, sequences threaded onto the structure exhibit common three-dimensional electrostatic and hydrophobic properties. These common physicochemical characteristics constitute a pharmacophoric footprint that promises to be useful in the design of a synthetic antigen for vaccine development.
authors.affiliation: Computational Molecular Biophysics, Interdisciplinary Center for Computational Science (IWR), University of Heidelberg, Im Neuenheimer Feld 368, 69120 Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Pisterer
authors.forename: Dan
authors.initials: D
authors.lastname: Mihailescu
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Smith
authors.forename: Jennifer
authors.initials: J
authors.lastname: Reed
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry*; D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000737:chemistry; D004560:Electricity; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D016915:AIDS Vaccines; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010455:Peptides