Document 0687
 DOCN  M9590687
 TI    Molecular Dynamics Simulation of a Leucine Zipper Motif Predicted for
       the Integrase of Human Immunodeficiency Virus Type I.
 DT    9509
 AU    Wang CY; Yang CF; Lai MC; Lee YH; Lee TL; Lin TH; National Tsing Hua
       University, Taiwan, R.O.C.
 SO    NIH Conf Retroviral Integrase. 1995 Jan 19-20;:(Participants' abstracts
       and posters, abstract no. 10a). Unique Identifier : AIDSLINE
       AIDS/95920032
 AB    We have used the molecular dynamics (MD) simulation package AMBER4 to
       search the conformation of a peptide predicted as a leucine zipper motif
       for the human immunodeficiency virus type I integrase protein (HIV
       IN-LZM). The peptide is composed of 22 amino acid residues and its
       location is from Val 151 to Leu 172. The searching procedure also
       includes two known alpha-helices that served as positive controls-
       namely; a 22-residue GCN4-p1 LZM and a 20-residue poly (L- alanine)
       (PLA). A 21-residue peptide extracted from a cytochrome C crystal
       (CCC-t) with determined conformation as a beta-turn is also included as
       a negative control. At the beginning of the search, two starting
       conformations-namely; the standard right-handed alpha-helix and the
       fully stretched conformations-are generated for each peptide. Structures
       generated as standard alpha-helix are equilibrated at room temperature
       for 90 ps while structures generated as a fully stretched one are
       equilibrated at 600 K for 120 ps. The CCC-t and PLA helices are nearly
       destroyed from the beginning of equilibration. However, for both the HIV
       IN-LZM and the GCN4-p1 LZM structures, there is substantial helicity
       being retained throughout the entire course of equilibration. Although
       helix propagation profiles calculated indicate that both peptides
       possess about the same propensity to form an alpha-helix, the HIV IN-LZM
       helix appears to be more stable than the GCN4-p1 one as judged by a
       variety of analyses on both structures generated during the
       equilibration course. The fact that predicted HIV IN-LZM can exist as an
       alpha-helix is also supported by the results of high temperature
       equilibration run on the fully stretched structures generated. In this
       run, the root-mean-square (RMS) deviations between the backbone atoms of
       the structures with the lowest potential energy (PE) identified within
       every 2 ps and the structure with the lowest PE searched in the same
       course of simulation are calculated. For both the HIV IN-LZM and the
       GCN4-p1 LZM, these RMS values decrease with the decrease of PE, which
       indicates that both structures are closer in conformations as their PEs
       are moved deeper into the PE well. This work has been published in
       BIOPOLYMER (34, 1027- 1036, 1994) recently. We are using circular
       dichroism and NM spectroscopy to examine the solution structure of the
       HIV IN-LZM peptide synthesized. This will serve as a first step of our
       goal to identify a possible coiled-coil domain for IN.
 DE    Cell Line  DNA Nucleotidyltransferases/GENETICS  DNA, Viral/*GENETICS
       Gene Products, gag/METABOLISM  Genes, tat  HIV Long Terminal Repeat
       HIV-1/ENZYMOLOGY/*GENETICS/PHYSIOLOGY  Human  Mutation
       Proviruses/GENETICS  T-Lymphocytes/VIROLOGY  Virus Integration/*GENETICS
       Virus Replication/GENETICS  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).