Molecular dynamics simulations of native and substrate-bound lysozyme. A study of the average structures and atomic fluctuations

J Mol Biol. 1986 Aug 5;190(3):455-79. doi: 10.1016/0022-2836(86)90015-x.

Abstract

Molecular dynamics simulations of hen egg-white lysozyme in the free and substrate-bound states are reported and the nature of the average structures and atomic fluctuations are analyzed. Crystallographic water molecules of structural importance, as determined by hydrogen-bonding, were included in the simulations. Comparisons are made between the dynamics and the X-ray results for the atomic positions, the main-chain and side-chain dihedral angles, and the hydrogen-bonding geometry. Improvements over earlier simulations in the potential energy function and methodology resulted in stable trajectories with the C alpha co-ordinates within 1.5 A of the starting X-ray structure. Structural features analyzed in the simulations agreed well with the X-ray results except for some surface residues. The Asx chi 2 dihedral distribution and the geometry of hydrogen bonding at reverse turns show differences; possible causes are discussed. The relation between the magnitudes and time-scales of the residue fluctuations and secondary structural features, such as helices beta-sheets and coiled loops, is examined. Significant differences in the residue mobilities between the simulations of the free and substrate-bound states were found in a region of the enzyme that is in direct contact with the substrate and in a region that is distant from the active-site cleft. The dynamic behavior of the structural water molecules is analyzed by examining the correlation between the fluctuations of the water oxygens and the lysozyme heavy-atoms to which they are hydrogen-bonded.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Computer Simulation
  • Crystallography
  • Hydrogen Bonding
  • Models, Biological
  • Motion
  • Muramidase*
  • Protein Conformation
  • Water

Substances

  • Water
  • Muramidase