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Combining Laue diffraction and molecular dynamics to study enzyme intermediates

Nature Structural Biology volume 3, pages 590–595 (1996)Cite this article

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.

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Author information

Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center, A3-023, 1124 Columbia St., Seattle, Washington, 98104, USA

    Barry L. Stoddard

  2. Department of Biochemistry, The Chicago Medical School, 333 Green Bay Road, North Chicago, Illinois, 60064, USA

    Antony Dean

  3. Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, Argonne, Illinois, 60439, USA

    Paul A. Bash

Authors
  1. Barry L. Stoddard
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  2. Antony Dean
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  3. Paul A. Bash
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Stoddard, B., Dean, A. & Bash, P. Combining Laue diffraction and molecular dynamics to study enzyme intermediates. Nat Struct Mol Biol 3, 590–595 (1996). https://doi.org/10.1038/nsb0796-590

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