Document 0572
 DOCN  M9550572
 TI    Probing structure-function relationships in human immunodeficiency virus
       type 1 protease via molecular dynamics simulation.
 DT    9505
 AU    Harte WE Jr; Beveridge DL; Bristol-Myers Squibb, Pharmaceutical Research
       Institute,; Wallingford, Connecticut 06492.
 SO    Methods Enzymol. 1994;241:178-95. Unique Identifier : AIDSLINE
       MED/95157310
 AB    This chapter has focused on the application of molecular dynamics
       computer simulations and related molecular modeling techniques to the
       study of HIV protease structure and structure-function relationships.
       The abundance of crystallographic data provides ample experimental
       quantities (average structures, temperature factors, and hydrogen bond
       topography) to validate the computational techniques employed.
       Furthermore, these studies provide insight into the structure and
       functional energetics of HIV-1 protease that would be difficult or
       impossible to study experimentally. This chapter covers studies that
       investigate correlated motion between and within subunits of the
       protease, mutants of the protease that disrupt the tertiary structure
       and dimer formation, and studies of HIV-1 protease-inhibitor complexes
       that rationalize both the protonation state of the active site and the
       observed binding strength of these complexes. These studies demonstrate
       that MD is capable of contributing to our understanding of
       structure-function relationships and may aid in the design of potential
       therapeutics.
 DE    Amino Acid Sequence  Binding Sites  *Computer Simulation
       Crystallography, X-Ray  Hydrogen Bonding  HIV Protease/*CHEMISTRY  HIV
       Protease Inhibitors/CHEMISTRY/PHARMACOLOGY  HIV-1/*ENZYMOLOGY  *Models,
       Molecular  Molecular Sequence Data  Protein Binding  *Protein
       Conformation  Structure-Activity Relationship  JOURNAL ARTICLE  REVIEW
       REVIEW, TUTORIAL

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