Document 0163
 DOCN  M95A0163
 TI    Flap opening in HIV-1 protease simulated by 'activated' molecular
       dynamics.
 DT    9510
 AU    Collins JR; Burt SK; Erickson JW; Structural Biochemistry Program,
       Frederick Biomedical; Supercomputing Center, PRI/DynCorp, National
       Cancer Institute -; Frederick Cancer Research and Development Center,
       Maryland; 21702-1201, USA.
 SO    Nat Struct Biol. 1995 Apr;2(4):334-8. Unique Identifier : AIDSLINE
       MED/95316683
 AB    We have used an 'activated' molecular dynamics approach to simulate flap
       opening in HIV-1 protease. An initial impulse for flap opening was
       provided by applying harmonic constraints to non-flap residues. After an
       initial 'melting' phase, the two beta-hairpin structures that constitute
       the flaps opened to a 25 A gap within 200 ps of simulation. Analysis of
       backbone torsion angles suggests that flap opening is related to
       conformational changes at Lys 45, Met 46, Gly 52 and Phe 53. In
       contrast, similar molecular dynamics simulations on the M46I mutant,
       which is associated with drug resistance, indicates that this mutation
       stabilizes the flaps in a closed conformation.
 DE    Amino Acid Sequence  Comparative Study  Computer Simulation  Drug
       Resistance, Microbial  HIV Protease/*CHEMISTRY/METABOLISM  HIV Protease
       Inhibitors/CHEMISTRY/*PHARMACOLOGY  HIV-1/ENZYMOLOGY  Models, Molecular
       Mutagenesis, Site-Directed  Point Mutation  *Protein Conformation
       *Protein Structure, Secondary  Recombinant Proteins/ANTAGONISTS &
       INHIB/CHEMISTRY  JOURNAL ARTICLE

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