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Title: Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering

X-ray diffraction from protein crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering is limited to what is available in the mean electron density. The diffuse scattering arises from correlations in the electron density variations and therefore contains information about collective motions in proteins. Previous studies using molecular-dynamics (MD) simulations to model diffuse scattering have been hindered by insufficient sampling of the conformational ensemble. To overcome this issue, we have performed a 1.1-μs MD simulation of crystalline staphylococcal nuclease, providing 100-fold more sampling than previous studies. This simulation enables reproducible calculations of the diffuse intensity and predicts functionally important motions, including transitions among at least eight metastable states with different active-site geometries. The total diffuse intensity calculated using the MD model is highly correlated with the experimental data. In particular, there is excellent agreement for the isotropic component of the diffuse intensity, and substantial but weaker agreement for the anisotropic component. The decomposition of the MD model into protein and solvent components indicates that protein–solvent interactions contribute substantially to the overall diffuse intensity. In conclusion, diffuse scattering can be used to validate predictions from MD simulations and can provide information tomore » improve MD models of protein motions.« less
 [1] ;  [2] ;  [3] ;  [4] ;  [2] ;  [1]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. Univ. of California, San Francisco, CA (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
Publication Date:
Report Number(s):
Journal ID: ISSN 0027-8424
Grant/Contract Number:
AC52-06NA25396; GM095887; STC-1231306; 1P01GM063210; OD009180; GM110580
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 111; Journal Issue: 50; Journal ID: ISSN 0027-8424
National Academy of Sciences, Washington, DC (United States)
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org:
Country of Publication:
United States
diffuse scattering; protein crystallography; molecular-dynamics simulation; protein dynamics; staphylococcal nuclease; 59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
Alternate Identifier(s):
OSTI ID: 1221841; OSTI ID: 1321746