Document 0319
 DOCN  M94A0319
 TI    Molecular dynamics simulation of a leucine zipper motif predicted for
       the integrase of human immunodeficiency virus type 1.
 DT    9412
 AU    Wang CY; Yang CF; Lai MC; Lee YH; Lee TL; Lin TH; Institute of
       Biomedical Science, National Tsing Hua University,; Taiwan, Republic of
       China.
 SO    Biopolymers. 1994 Aug;34(8):1027-36. Unique Identifier : AIDSLINE
       MED/94355641
 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 1 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 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.
 DE    Amino Acid Sequence  *Computer Simulation  DNA
       Nucleotidyltransferases/*GENETICS  HIV-1/*ENZYMOLOGY  *Models, Molecular
       Molecular Sequence Data  Retroviridae Proteins/*GENETICS  Support,
       Non-U.S. Gov't  Thermodynamics  JOURNAL ARTICLE

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