title: The HF-SCF energy of HIV-1 MNgp120 V3 hairpin loop conformers.
abstract: The purpose of this study is to analyze the structure of the V3 loop of the HIV-1 gp120 molecule at the atomic level. The total energy of each member of the antibody-complexed 16-mer V3 conformer data set of Sharon et al. (PDB 1NJ0) was determined by the Hartree-Fock-self-consistent field (HF-SCF) method and with the GROMOS96 force field. There was no correlation between the results of the classical GROMOS96 force field analysis and the ab initio HF-SCF quantum mechanical analysis of the energy of the V3-loop-peptide conformers. HF-SCF optimization (AM1) of conformer geometries yielded structures in which HIS315 is displaced from its original position in the combining site of human antibody fragment 447-52D, but with the hairpin turn intact. The hairpin shape of the V3 loop remained detectable, albeit distorted, even with perturbation by a lithium dicationic electrostatic force field and by substitution of the PRO320 at the crown of the V3 hairpin by a GLY. These data suggest that the hairpin conformation is at least partially stable to long-range electrostatic perturbations, either with or without PRO in the tip of the crown of the V3-hairpin loop. [figure: see text]. Molecular geometry of HIV-1 V3 conformer model 5 and a GLY320 substituted model 5. Space-filling models were obtained with ViewMol3D [Sharon et al. (2002) PDB 1NJ0]). Red=oxygen, blue=nitrogen, black=carbon, white=hydrogen and purple=lithium. End-to-end distance (D) was obtained with ViewMol3D and is in Angstroms. Geometry optimized GLY320 Model 5, D=4.74 A.
authors.affiliation: Department of Medicine, Brown Medical School, Brown University, RI 02912, Providence, USA. joel_weltman@brown.edu
authors.forename: Joel K
authors.initials: JK
authors.lastname: Weltman
authors.forename: Gail
authors.initials: G
authors.lastname: Skowron
authors.forename: George B
authors.initials: GB
authors.lastname: Loriot
mesh_terms: D019295:Computational Biology / Q000379:methods; D015483:HIV Antibodies / Q000737:chemistry; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015497:HIV-1; D008958:Models, Molecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120