Combining Laue diffraction and molecular dynamics to study enzyme intermediates

Nat Struct Biol. 1996 Jul;3(7):590-5. doi: 10.1038/nsb0796-590.

Abstract

Two separate techniques, Laue diffraction and computational molecular dynamics (MD) simulations, have been independently developed to allow the visualization and assessment of transient structural states. Recent studies on isocitrate dehydrogenase show that computational MD simulations of an enzymatic Michaelis complex are consistent with difference Fourier electron density maps of the same structure from a Laue experiment. The use of independent MD studies during crystallographic refinement has allowed us to assign with confidence a number of additional contacts and features important for hydride transfer. We find that unrestrained independent MD simulations provides a very useful method of cross-validation for highly mobile atoms in regions of experimental density that are poorly defined. Likewise, information from Laue difference maps provides information about substrate conformation and interactions that greatly facilitate MD simulations.

Publication types

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

MeSH terms

  • Computer Simulation
  • Crystallography, X-Ray / methods*
  • Enzymes / chemistry*
  • Fourier Analysis
  • Isocitrate Dehydrogenase / chemistry
  • Models, Molecular*
  • Molecular Conformation
  • Stochastic Processes

Substances

  • Enzymes
  • Isocitrate Dehydrogenase