rdf-syntax-grammar
mods:
  schema location: http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
  title info:
    title: Molecular dynamics studies of porcine pancreatic elastase
    sub title: the native state and complexed to two trifluoroacetyl dipeptide anilide inhibitors
  name:
    name part: Carlson, Gail Marie.
    role:
      role term: creator
  name:
    name part: McCammon, J. Andrew
    role:
      role term: degree supervisor.
  name:
    name part: Meyer, Edgar
    role:
      role term: degree supervisor.
  name:
    name part: Pace, C. N.
    role:
      role term: degree committee member.
  name:
    name part: Sander, Eugene G.
    role:
      role term: degree committee member.
  name:
    name part: Scott, A. Ian
    role:
      role term: degree committee member.
  name:
    name part: Texas A & M University
    role:
      role term: degree granting institution.
  type of resource: text
  genre: bibliography
  genre: Academic theses
  origin info:
    place:
      place term: xx
    date issued: 1987
    issuance: monographic
  language:
    language term: eng
  physical description:
    form: print
    extent: xv, 229 leaves : illustrations ; 29 cm
  abstract: Molecular dynamics simulations of the serine protease porcine pancreatic elastase in the native state (in vacuo and solvated) and complexed to two trifluoroacetyl dipeptide inhibitors are reported. Crystallographically resolved water molecules were included in all calculations, and for two of the simulations the active site was solvated through application of a "dome" of water molecules. The form of the interaction potential energy function and a procedure for deriving parameters to use with it are discussed. Comparisons are made between the molecular dynamics results and available high-resolution X-ray data with respect to radii of gyration, atomic positions, positional fluctuations, dihedral angles (φ, ψ and ω) and hydrogen bonding pattern. The magnitudes and time development of residue motions with respect to their involvement in particular secondary structure (α-helices, β-sheets, β-turns, loops) are also examined. Structural features of the simulations agreed well with the X-ray structure with the exception of residues involved in β-turn geometries. Some damping of motions was observed in the case of the solvated simulations. Positional fluctuations of residues in the free and bound states are compared and it is found that the bound molecules have a global increase in motion and that this increase is particularly dramatic in the S₂-->S₄ regions of the active site where the ligand molecule is bound. In hopes of rationalizing the high inhibitory power of these nonproductively bound ligands, the active site dynamics (involving the serine-histidine-aspartate triad) of the solvated native enzyme and the trifluoroacetyl-l-lysyl-l-alanyl-p-trifluoroisopropyl anilide complex were examined. Crystallographic and NMR results indicate a conformational shift of the catalytic histidine residue such that it exhibits an improved hydrogen bonding interaction with the catalytic serine residue in the active site. Because this shift does not occur with the less potent acetylated i…
  note: Typescript (photocopy).
  note: Vita.
  note: Ph. D. in Biochemistry Texas A & M University 1987
  note: Includes bibliographical references (leaves 217-228).
  subject:
    topic: Molecular dynamics
  subject:
    topic: Elastases
    topic: Structure-activity relationships
  subject:
    topic: Proteolytic enzymes
  subject:
    topic: Major biochemistry
  identifier: http://proxy.library.tamu.edu/login
  related item:
    location:
      url: http://proxy.library.tamu.edu/login
  record info:
    record content source: TXA
    record creation date: 880929
    record change date: 20200904152403.0
    record identifier: in00000734422
    language of cataloging:
      language term: eng