Internal protein motions in molecular-dynamics simulations of Bragg and diffuse X-ray scattering
Abstract
Molecular-dynamics (MD) simulations of Bragg and diffuse X-ray scattering provide a means of obtaining experimentally validated models of protein conformational ensembles. This paper shows that compared with a single periodic unit-cell model, the accuracy of simulating diffuse scattering is increased when the crystal is modeled as a periodic supercell consisting of a 2 × 2 × 2 layout of eight unit cells. The MD simulations capture the general dependence of correlations on the separation of atoms. There is substantial agreement between the simulated Bragg reflections and the crystal structure; there are local deviations, however, indicating both the limitation of using a single structure to model disordered regions of the protein and local deviations of the average structure away from the crystal structure. Although it was anticipated that a simulation of longer duration might be required to achieve maximal agreement of the diffuse scattering calculation with the data using the supercell model, only a microsecond is required, the same as for the unit cell. Rigid protein motions only account for a minority fraction of the variation in atom positions from the simulation. The results indicate that protein crystal dynamics may be dominated by internal motions rather than packing interactions, and that MD simulations canmore »
- Authors:
-
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); USDOE National Nuclear Security Administration (NNSA); Univ. of California, Los Angeles, CA (United States)
- OSTI Identifier:
- 1418076
- Alternate Identifier(s):
- OSTI ID: 1427377
- Report Number(s):
- LA-UR-17-27716
Journal ID: ISSN 2052-2525; IUCRAJ; PII: S2052252518000519
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Published Article
- Journal Name:
- IUCrJ
- Additional Journal Information:
- Journal Name: IUCrJ Journal Volume: 5 Journal Issue: 2; Journal ID: ISSN 2052-2525
- Publisher:
- International Union of Crystallography
- Country of Publication:
- United Kingdom
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 97 MATHEMATICS AND COMPUTING; Biological Science; diffuse scattering; protein crystallography; X-ray diffraction; molecular dynamics simulation; protein conformational ensemble; staphylococcal nuclease
Citation Formats
Wall, Michael E. Internal protein motions in molecular-dynamics simulations of Bragg and diffuse X-ray scattering. United Kingdom: N. p., 2018.
Web. doi:10.1107/S2052252518000519.
Wall, Michael E. Internal protein motions in molecular-dynamics simulations of Bragg and diffuse X-ray scattering. United Kingdom. https://doi.org/10.1107/S2052252518000519
Wall, Michael E. Thu .
"Internal protein motions in molecular-dynamics simulations of Bragg and diffuse X-ray scattering". United Kingdom. https://doi.org/10.1107/S2052252518000519.
@article{osti_1418076,
title = {Internal protein motions in molecular-dynamics simulations of Bragg and diffuse X-ray scattering},
author = {Wall, Michael E.},
abstractNote = {Molecular-dynamics (MD) simulations of Bragg and diffuse X-ray scattering provide a means of obtaining experimentally validated models of protein conformational ensembles. This paper shows that compared with a single periodic unit-cell model, the accuracy of simulating diffuse scattering is increased when the crystal is modeled as a periodic supercell consisting of a 2 × 2 × 2 layout of eight unit cells. The MD simulations capture the general dependence of correlations on the separation of atoms. There is substantial agreement between the simulated Bragg reflections and the crystal structure; there are local deviations, however, indicating both the limitation of using a single structure to model disordered regions of the protein and local deviations of the average structure away from the crystal structure. Although it was anticipated that a simulation of longer duration might be required to achieve maximal agreement of the diffuse scattering calculation with the data using the supercell model, only a microsecond is required, the same as for the unit cell. Rigid protein motions only account for a minority fraction of the variation in atom positions from the simulation. The results indicate that protein crystal dynamics may be dominated by internal motions rather than packing interactions, and that MD simulations can be combined with Bragg and diffuse X-ray scattering to model the protein conformational ensemble.},
doi = {10.1107/S2052252518000519},
journal = {IUCrJ},
number = 2,
volume = 5,
place = {United Kingdom},
year = {Thu Jan 25 00:00:00 EST 2018},
month = {Thu Jan 25 00:00:00 EST 2018}
}
https://doi.org/10.1107/S2052252518000519
Web of Science
Works referenced in this record:
Validation of Molecular Dynamics Simulations of Biomolecules Using NMR Spin Relaxation as Benchmarks: Application to the AMBER99SB Force Field
journal, March 2007
- Showalter, Scott A.; Brüschweiler, Rafael
- Journal of Chemical Theory and Computation, Vol. 3, Issue 3
SwissParam: A fast force field generation tool for small organic molecules
journal, May 2011
- Zoete, Vincent; Cuendet, Michel A.; Grosdidier, Aurélien
- Journal of Computational Chemistry, Vol. 32, Issue 11
Evaluating Elastic Network Models of Crystalline Biological Molecules with Temperature Factors, Correlated Motions, and Diffuse X-Ray Scattering
journal, October 2010
- Riccardi, Demian; Cui, Qiang; Phillips, George N.
- Biophysical Journal, Vol. 99, Issue 8
Molecular Rigid-Body Displacements in a Tetragonal Lysozyme Crystal Confirmed by X-ray Diffuse Scattering
journal, July 1996
- Pérez, J.; Faure, P.; Benoit, J. -P.
- Acta Crystallographica Section D Biological Crystallography, Vol. 52, Issue 4
Slow conformational exchange and overall rocking motion in ubiquitin protein crystals
journal, July 2017
- Kurauskas, Vilius; Izmailov, Sergei A.; Rogacheva, Olga N.
- Nature Communications, Vol. 8, Issue 1
Overview of the CCP 4 suite and current developments
journal, March 2011
- Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
Atomic-Resolution Structural Dynamics in Crystalline Proteins from NMR and Molecular Simulation
journal, November 2012
- Mollica, Luca; Baias, Maria; Lewandowski, Józef R.
- The Journal of Physical Chemistry Letters, Vol. 3, Issue 23
GROMACS: A message-passing parallel molecular dynamics implementation
journal, September 1995
- Berendsen, H. J. C.; van der Spoel, D.; van Drunen, R.
- Computer Physics Communications, Vol. 91, Issue 1-3
Extending the treatment of backbone energetics in protein force fields: Limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations
journal, August 2004
- Mackerell, Alexander D.; Feig, Michael; Brooks, Charles L.
- Journal of Computational Chemistry, Vol. 25, Issue 11
Correlations of atomic movements in lysozyme crystals
journal, February 1992
- Clarage, James B.; Clarage, Michael S.; Phillips, Walter C.
- Proteins: Structure, Function, and Genetics, Vol. 12, Issue 2
Correlated intramolecular motions and diffuse x–ray scattering in lysozyme
journal, February 1994
- Faure, P.; Micu, A.; Pérahia, D.
- Nature Structural & Molecular Biology, Vol. 1, Issue 2
Application of Elastic Network Models to Proteins in the Crystalline State
journal, January 2009
- Riccardi, Demian; Cui, Qiang; Phillips, George N.
- Biophysical Journal, Vol. 96, Issue 2
Variations on a theme by Debye and Waller: From simple crystals to proteins
journal, October 1997
- García, Angel E.; Krumhansl, James A.; Frauenfelder, Hans
- Proteins: Structure, Function, and Genetics, Vol. 29, Issue 2
Improved side-chain torsion potentials for the Amber ff99SB protein force field
journal, January 2010
- Lindorff-Larsen, Kresten; Piana, Stefano; Palmo, Kim
- Proteins: Structure, Function, and Bioinformatics
Acoustic vibrations contribute to the diffuse scatter produced by ribosome crystals
journal, September 2015
- Polikanov, Yury S.; Moore, Peter B.
- Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 10
Dynamics of Proteins in Crystals: Comparison of Experiment with Simple Models
journal, August 2002
- Kundu, Sibsankar; Melton, Julia S.; Sorensen, Dan C.
- Biophysical Journal, Vol. 83, Issue 2
Protein dynamics from X-ray crystallography: Anisotropic, global motion in diffuse scattering patterns
journal, December 2006
- Meinhold, Lars; Smith, Jeremy C.
- Proteins: Structure, Function, and Bioinformatics, Vol. 66, Issue 4
Molecular Dynamics of Staphylococcal Nuclease: Comparison of Simulation with 15 N and 13 C NMR Relaxation Data
journal, June 1998
- Chatfield, David C.; Szabo, Attila; Brooks, Bernard R.
- Journal of the American Chemical Society, Vol. 120, Issue 21
Peptide Crystal Simulations Reveal Hidden Dynamics
journal, May 2013
- Janowski, Pawel A.; Cerutti, David S.; Holton, James
- Journal of the American Chemical Society, Vol. 135, Issue 21
The crystal structure of the ternary complex of staphylococcal nuclease, Ca2+ and the inhibitor pdTp, refined at 1.65 Å
journal, January 1989
- Loll, Patrick J.; Lattman, Eaton E.
- Proteins: Structure, Function, and Genetics, Vol. 5, Issue 3
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
Systematic Validation of Protein Force Fields against Experimental Data
journal, February 2012
- Lindorff-Larsen, Kresten; Maragakis, Paul; Piana, Stefano
- PLoS ONE, Vol. 7, Issue 2
The Computational Crystallography Toolbox : crystallographic algorithms in a reusable software framework
journal, January 2002
- Grosse-Kunstleve, Ralf W.; Sauter, Nicholas K.; Moriarty, Nigel W.
- Journal of Applied Crystallography, Vol. 35, Issue 1
Three-dimensional diffuse x-ray scattering from crystals of Staphylococcal nuclease
journal, June 1997
- Wall, M. E.; Ealick, S. E.; Gruner, S. M.
- Proceedings of the National Academy of Sciences, Vol. 94, Issue 12
All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins †
journal, April 1998
- MacKerell, A. D.; Bashford, D.; Bellott, M.
- The Journal of Physical Chemistry B, Vol. 102, Issue 18
Fluctuations and Correlations in Crystalline Protein Dynamics: A Simulation Analysis of Staphylococcal Nuclease
journal, April 2005
- Meinhold, Lars; Smith, Jeremy C.
- Biophysical Journal, Vol. 88, Issue 4
Molecular dynamics studied by analysis of the X-ray diffuse scattering from lysozyme crystals
journal, February 1987
- Doucet, J.; Benoit, J. P.
- Nature, Vol. 325, Issue 6105
Motions of calmodulin characterized using both Bragg and diffuse X-ray scattering
journal, December 1997
- Wall, Michael E.; Clarage, James B.; Phillips, George N.
- Structure, Vol. 5, Issue 12
Modelling dynamics in protein crystal structures by ensemble refinement
journal, December 2012
- Burnley, B. Tom; Afonine, Pavel V.; Adams, Paul D.
- eLife, Vol. 1
Molecular dynamics simulation of triclinic lysozyme in a crystal lattice: Molecular Dynamics of Crystal Lysozyme
journal, June 2015
- Janowski, Pawel A.; Liu, Chunmei; Deckman, Jason
- Protein Science, Vol. 25, Issue 1
X-ray diffuse scattering and rigid-body motion in crystalline lysozyme probed by molecular dynamics simulation 1 1Edited by R. Huber
journal, May 1998
- Héry, Stéphanie; Genest, Daniel; Smith, Jeremy C.
- Journal of Molecular Biology, Vol. 279, Issue 1
Macromolecular diffractive imaging using imperfect crystals
journal, February 2016
- Ayyer, Kartik; Yefanov, Oleksandr M.; Oberthür, Dominik
- Nature, Vol. 530, Issue 7589, p. 202-206
Correlated Dynamics Determining X-Ray Diffuse Scattering from a Crystalline Protein Revealed by Molecular Dynamics Simulation
journal, November 2005
- Meinhold, Lars; Smith, Jeremy C.
- Physical Review Letters, Vol. 95, Issue 21
A sampling problem in molecular dynamics simulations of macromolecules.
journal, April 1995
- Clarage, J. B.; Romo, T.; Andrews, B. K.
- Proceedings of the National Academy of Sciences, Vol. 92, Issue 8
Crystallographic fast Fourier transforms
journal, March 1973
- Ten Eyck, L. F.
- Acta Crystallographica Section A, Vol. 29, Issue 2
Observing the overall rocking motion of a protein in a crystal
journal, October 2015
- Ma, Peixiang; Xue, Yi; Coquelle, Nicolas
- Nature Communications, Vol. 6, Issue 1
Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering
journal, December 2014
- Wall, Michael E.; Van Benschoten, Andrew H.; Sauter, Nicholas K.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 50