Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering
Abstract
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. Decomposition of the MD model into protein and solvent components indicates that protein–solvent interactions contribute substantially to the overall diffuse intensity. We conclude that diffuse scattering can be used to validate predictions from MD simulations and can provide information tomore »
- Authors:
-
- Computer, Computational, and Statistical Sciences Division and
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158,
- Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, and
- Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, and, Department of Bioengineering, University of California, Berkeley, CA 94720
- Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545,
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1235104
- Alternate Identifier(s):
- OSTI ID: 1221841; OSTI ID: 1321746
- Report Number(s):
- LA-UR-14-26310
Journal ID: ISSN 0027-8424
- Grant/Contract Number:
- AC52-06NA25396; GM095887; STC-1231306; 1P01GM063210; OD009180; GM110580
- Resource Type:
- Published Article
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 111 Journal Issue: 50; Journal ID: ISSN 0027-8424
- Publisher:
- Proceedings of the National Academy of Sciences
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; diffuse scattering; protein crystallography; molecular-dynamics simulation; protein dynamics; staphylococcal nuclease
Citation Formats
Wall, Michael E., Van Benschoten, Andrew H., Sauter, Nicholas K., Adams, Paul D., Fraser, James S., and Terwilliger, Thomas C. Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering. United States: N. p., 2014.
Web. doi:10.1073/pnas.1416744111.
Wall, Michael E., Van Benschoten, Andrew H., Sauter, Nicholas K., Adams, Paul D., Fraser, James S., & Terwilliger, Thomas C. Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering. United States. https://doi.org/10.1073/pnas.1416744111
Wall, Michael E., Van Benschoten, Andrew H., Sauter, Nicholas K., Adams, Paul D., Fraser, James S., and Terwilliger, Thomas C. Tue .
"Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering". United States. https://doi.org/10.1073/pnas.1416744111.
@article{osti_1235104,
title = {Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering},
author = {Wall, Michael E. and Van Benschoten, Andrew H. and Sauter, Nicholas K. and Adams, Paul D. and Fraser, James S. and Terwilliger, Thomas C.},
abstractNote = {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. Decomposition of the MD model into protein and solvent components indicates that protein–solvent interactions contribute substantially to the overall diffuse intensity. We conclude that diffuse scattering can be used to validate predictions from MD simulations and can provide information to improve MD models of protein motions.},
doi = {10.1073/pnas.1416744111},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 50,
volume = 111,
place = {United States},
year = {Tue Dec 16 00:00:00 EST 2014},
month = {Tue Dec 16 00:00:00 EST 2014}
}
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