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

Wall, Michael E.; Van Benschoten, Andrew H.; Sauter, Nicholas K.; Adams, Paul D.; Fraser, James S.; Terwilliger, Thomas C.

doi:10.1073/pnas.1416744111

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

Journal Article · Tue Dec 16 00:00:00 EST 2014 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1416744111· OSTI ID:1235104

Wall, Michael E. ^[1]; Van Benschoten, Andrew H. ^[2]; Sauter, Nicholas K. ^[3]; Adams, Paul D. ^[4]; Fraser, James S. ^[2]; Terwilliger, Thomas C. ^[5]

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,

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC52-06NA25396; GM095887; STC-1231306; 1P01GM063210; OD009180; GM110580

OSTI ID:: 1235104

Alternate ID(s):: OSTI ID: 1221841; OSTI ID: 1321746

Report Number(s):: LA-UR-14-26310

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 111 Journal Issue: 50; ISSN 0027-8424

Publisher:: Proceedings of the National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 42 works

Citation information provided by
Web of Science

References (61)

Hidden alternative structures of proline isomerase essential for catalysis Fraser, James S.; Clarkson, Michael W.; Degnan, Sheena C. Nature, Vol. 462, Issue 7273 https://doi.org/10.1038/nature08615	journal	December 2009
Diffuse x-ray scattering from tropomyosin crystals Chacko, S.; Phillips, G. N. Biophysical Journal, Vol. 61, Issue 5 https://doi.org/10.1016/S0006-3495(92)81934-3	journal	May 1992
Validation of Molecular Dynamics Simulations of Biomolecules Using NMR Spin Relaxation as Benchmarks: Application to the AMBER99SB Force Field Showalter, Scott A.; Brüschweiler, Rafael Journal of Chemical Theory and Computation, Vol. 3, Issue 3 https://doi.org/10.1021/ct7000045	journal	March 2007
Evaluating Elastic Network Models of Crystalline Biological Molecules with Temperature Factors, Correlated Motions, and Diffuse X-Ray Scattering Riccardi, Demian; Cui, Qiang; Phillips, George N. Biophysical Journal, Vol. 99, Issue 8 https://doi.org/10.1016/j.bpj.2010.08.013	journal	October 2010
Are Protein Force Fields Getting Better? A Systematic Benchmark on 524 Diverse NMR Measurements Beauchamp, Kyle A.; Lin, Yu-Shan; Das, Rhiju Journal of Chemical Theory and Computation, Vol. 8, Issue 4 https://doi.org/10.1021/ct2007814	journal	March 2012
Dynamics of Carbon Monoxide Binding by Heme Proteins Austin, R. H.; Beeson, K.; Eisenstein, L. Science, Vol. 181, Issue 4099 https://doi.org/10.1126/science.181.4099.541	journal	August 1973
Correlations of atomic movements in lysozyme crystals Clarage, James B.; Clarage, Michael S.; Phillips, Walter C. Proteins: Structure, Function, and Genetics, Vol. 12, Issue 2 https://doi.org/10.1002/prot.340120208	journal	February 1992
Correlated intramolecular motions and diffuse x–ray scattering in lysozyme Faure, P.; Micu, A.; Pérahia, D. Nature Structural & Molecular Biology, Vol. 1, Issue 2 https://doi.org/10.1038/nsb0294-124	journal	February 1994
Heterogeneity and Inaccuracy in Protein Structures Solved by X-Ray Crystallography DePristo, Mark A.; de Bakker, Paul I. W.; Blundell, Tom L. Structure, Vol. 12, Issue 5 https://doi.org/10.1016/j.str.2004.02.031	journal	May 2004
Is one solution good enough? Furnham, Nicholas; Blundell, Tom L.; DePristo, Mark A. Nature Structural & Molecular Biology, Vol. 13, Issue 3 https://doi.org/10.1038/nsmb0306-184	journal	March 2006
Analysis of diffuse scattering from yeast initiator tRNA crystals Kolatkar, A. R.; Clarage, J. B.; Phillips Jnr, G. N. Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 2 https://doi.org/10.1107/S0907444993011692	journal	March 1994
Protein dynamics: use of computer graphics and protein crystal diffuse scattering recorded with synchrotron X-radiation Helliwell, J. R.; Glover, I. D.; Jones, A. Biochemical Society Transactions, Vol. 14, Issue 3 https://doi.org/10.1042/bst0140653	journal	June 1986
Staphylococcal nuclease: Proposed mechanism of action based on structure of enzyme--thymidine 3',5'-bisphosphate--calcium ion complex at 1.5-A resolution Cotton, F. A.; Hazen, E. E.; Legg, M. J. Proceedings of the National Academy of Sciences, Vol. 76, Issue 6 https://doi.org/10.1073/pnas.76.6.2551	journal	June 1979
The crystal structure of staphylococcal nuclease refined at 1.7 Å resolution Hynes, Thomas R.; Fox, Robert O. Proteins: Structure, Function, and Genetics, Vol. 10, Issue 2 https://doi.org/10.1002/prot.340100203	journal	February 1991
Improved side-chain torsion potentials for the Amber ff99SB protein force field Lindorff-Larsen, Kresten; Piana, Stefano; Palmo, Kim Proteins: Structure, Function, and Bioinformatics https://doi.org/10.1002/prot.22711	journal	January 2010
The Activity of an Enzyme in the Crystalline State: Ribonuclease S Doscher, Marilynn S.; Richards, Frederic M. Journal of Biological Chemistry, Vol. 238, Issue 7 https://doi.org/10.1016/S0021-9258(19)67984-6	journal	July 1963
Collective motions in proteins investigated by X-ray diffuse scattering Mizuguchi, Kenji; Kidera, Akinori; Gō, Nobuhiro Proteins: Structure, Function, and Genetics, Vol. 18, Issue 1 https://doi.org/10.1002/prot.340180106	journal	January 1994
Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides ^† Kaminski, George A.; Friesner, Richard A.; Tirado-Rives, Julian The Journal of Physical Chemistry B, Vol. 105, Issue 28 https://doi.org/10.1021/jp003919d	journal	July 2001
Dynamic information from protein crystallography Sternberg, M. J. E.; Grace, D. E. P.; Phillips, D. C. Journal of Molecular Biology, Vol. 130, Issue 3 https://doi.org/10.1016/0022-2836(79)90539-4	journal	May 1979
Highly constrained multiple-copy refinement of protein crystal structures Pellegrini, Matteo; Grønbech-Jensen, Niels; Kelly, Jennifer A. Proteins: Structure, Function, and Genetics, Vol. 29, Issue 4 https://doi.org/10.1002/(SICI)1097-0134(199712)29:4<426::AID-PROT3>3.0.CO;2-6	journal	December 1997
Liquid-like movements in crystalline insulin Caspar, D. L. D.; Clarage, J.; Salunke, D. M. Nature, Vol. 332, Issue 6165 https://doi.org/10.1038/332659a0	journal	April 1988
The variety of X-ray diffuse scattering from macromolecular crystals and its respective components Glover, I. D.; Harris, G. W.; Helliwell, J. R. Acta Crystallographica Section B Structural Science, Vol. 47, Issue 6 https://doi.org/10.1107/S0108768191004585	journal	December 1991
Rigid protein motion as a model for crystallographic temperature factors. Kuriyan, J.; Weis, W. I. Proceedings of the National Academy of Sciences, Vol. 88, Issue 7 https://doi.org/10.1073/pnas.88.7.2773	journal	April 1991
Molecular dynamics studied by analysis of the X-ray diffuse scattering from lysozyme crystals Doucet, J.; Benoit, J. P. Nature, Vol. 325, Issue 6105 https://doi.org/10.1038/325643a0	journal	February 1987
Lattice Dynamics of a Protein Crystal Meinhold, Lars; Merzel, Franci; Smith, Jeremy C. Physical Review Letters, Vol. 99, Issue 13 https://doi.org/10.1103/PhysRevLett.99.138101	journal	September 2007
Motions of calmodulin characterized using both Bragg and diffuse X-ray scattering Wall, Michael E.; Clarage, James B.; Phillips, George N. Structure, Vol. 5, Issue 12 https://doi.org/10.1016/S0969-2126(97)00308-0	journal	December 1997
Modelling dynamics in protein crystal structures by ensemble refinement Burnley, B. Tom; Afonine, Pavel V.; Adams, Paul D. eLife, Vol. 1 https://doi.org/10.7554/eLife.00311	journal	December 2012
X-ray diffuse scattering and rigid-body motion in crystalline lysozyme probed by molecular dynamics simulation 1 1Edited by R. Huber Héry, Stéphanie; Genest, Daniel; Smith, Jeremy C. Journal of Molecular Biology, Vol. 279, Issue 1 https://doi.org/10.1006/jmbi.1998.1754	journal	May 1998
Biomolecular Simulation: A Computational Microscope for Molecular Biology Dror, Ron O.; Dirks, Robert M.; Grossman, J. P. Annual Review of Biophysics, Vol. 41, Issue 1 https://doi.org/10.1146/annurev-biophys-042910-155245	journal	June 2012
Parallel tempering: Theory, applications, and new perspectives Earl, David J.; Deem, Michael W. Physical Chemistry Chemical Physics, Vol. 7, Issue 23 https://doi.org/10.1039/b509983h	journal	January 2005
Everything you wanted to know about Markov State Models but were afraid to ask Pande, Vijay S.; Beauchamp, Kyle; Bowman, Gregory R. Methods, Vol. 52, Issue 1 https://doi.org/10.1016/j.ymeth.2010.06.002	journal	September 2010
Visualizing networks of mobility in proteins Wilson, Mark A. Nature Methods, Vol. 10, Issue 9 https://doi.org/10.1038/nmeth.2606	journal	August 2013
Staphylococcal nuclease active-site amino acids: pH dependence of tyrosines and arginines by carbon-13 NMR and correlation with kinetic studies Grissom, Charles B.; Markley, John L. Biochemistry, Vol. 28, Issue 5 https://doi.org/10.1021/bi00431a023	journal	March 1989
Exploring the Structural Dynamics of the E.coli Chaperonin GroEL Using Translation-libration-screw Crystallographic Refinement of Intermediate States Chaudhry, Charu; Horwich, Arthur L.; Brunger, Axel T. Journal of Molecular Biology, Vol. 342, Issue 1 https://doi.org/10.1016/j.jmb.2004.07.015	journal	September 2004
Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids Jorgensen, William L.; Maxwell, David S.; Tirado-Rives, Julian Journal of the American Chemical Society, Vol. 118, Issue 45 https://doi.org/10.1021/ja9621760	journal	January 1996
Conformational Substates in Proteins Frauenfelder, H.; Parak, F.; Young, R. D. Annual Review of Biophysics and Biophysical Chemistry, Vol. 17, Issue 1 https://doi.org/10.1146/annurev.bb.17.060188.002315	journal	June 1988
Sublattice parallel replica dynamics Martínez, Enrique; Uberuaga, Blas P.; Voter, Arthur F. Physical Review E, Vol. 89, Issue 6 https://doi.org/10.1103/PhysRevE.89.063308	journal	June 2014
GROMACS: A message-passing parallel molecular dynamics implementation Berendsen, H. J. C.; van der Spoel, D.; van Drunen, R. Computer Physics Communications, Vol. 91, Issue 1-3 https://doi.org/10.1016/0010-4655(95)00042-E	journal	September 1995
Variations on a theme by Debye and Waller: From simple crystals to proteins García, Angel E.; Krumhansl, James A.; Frauenfelder, Hans Proteins: Structure, Function, and Genetics, Vol. 29, Issue 2 https://doi.org/10.1002/(SICI)1097-0134(199710)29:2<153::AID-PROT3>3.0.CO;2-E	journal	October 1997
Ligand binding and internal equilibiums in proteins Weber, Gregorio Biochemistry, Vol. 11, Issue 5 https://doi.org/10.1021/bi00755a028	journal	February 1972
Temperature-dependent X-ray diffraction as a probe of protein structural dynamics Frauenfelder, Hans; Petsko, Gregory A.; Tsernoglou, Demetrius Nature, Vol. 280, Issue 5723 https://doi.org/10.1038/280558a0	journal	August 1979
Conformational Disorder of Proteins Assessed by Real-Space Molecular Dynamics Refinement Chen, Zhi; Chapman, Michael S. Biophysical Journal, Vol. 80, Issue 3 https://doi.org/10.1016/S0006-3495(01)76118-8	journal	March 2001
Motions of tropomyosin. Crystal as metaphor Phillips, G. N.; Fillers, J. P.; Cohen, C. Biophysical Journal, Vol. 32, Issue 1 https://doi.org/10.1016/S0006-3495(80)84985-X	journal	October 1980
Protein dynamics from X-ray crystallography: Anisotropic, global motion in diffuse scattering patterns Meinhold, Lars; Smith, Jeremy C. Proteins: Structure, Function, and Bioinformatics, Vol. 66, Issue 4 https://doi.org/10.1002/prot.21246	journal	December 2006
Molecular Dynamics of Staphylococcal Nuclease: Comparison of Simulation with ¹⁵ N and ¹³ C NMR Relaxation Data Chatfield, David C.; Szabo, Attila; Brooks, Bernard R. Journal of the American Chemical Society, Vol. 120, Issue 21 https://doi.org/10.1021/ja972215n	journal	June 1998
X-ray refinement significantly underestimates the level of microscopic heterogeneity in biomolecular crystals Kuzmanic, Antonija; Pannu, Navraj S.; Zagrovic, Bojan Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4220	journal	February 2014
Peptide Crystal Simulations Reveal Hidden Dynamics Janowski, Pawel A.; Cerutti, David S.; Holton, James Journal of the American Chemical Society, Vol. 135, Issue 21 https://doi.org/10.1021/ja401382y	journal	May 2013
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Systematic Validation of Protein Force Fields against Experimental Data Lindorff-Larsen, Kresten; Maragakis, Paul; Piana, Stefano PLoS ONE, Vol. 7, Issue 2 https://doi.org/10.1371/journal.pone.0032131	journal	February 2012
Three-dimensional diffuse x-ray scattering from crystals of Staphylococcal nuclease Wall, M. E.; Ealick, S. E.; Gruner, S. M. Proceedings of the National Academy of Sciences, Vol. 94, Issue 12 https://doi.org/10.1073/pnas.94.12.6180	journal	June 1997
The Computational Crystallography Toolbox : crystallographic algorithms in a reusable software framework Grosse-Kunstleve, Ralf W.; Sauter, Nicholas K.; Moriarty, Nigel W. Journal of Applied Crystallography, Vol. 35, Issue 1 https://doi.org/10.1107/S0021889801017824	journal	January 2002
Fluctuations and Correlations in Crystalline Protein Dynamics: A Simulation Analysis of Staphylococcal Nuclease Meinhold, Lars; Smith, Jeremy C. Biophysical Journal, Vol. 88, Issue 4 https://doi.org/10.1529/biophysj.104.056101	journal	April 2005
Exploration of disorder in protein structures by X-ray restrained molecular dynamics Kuriyan, John; Ösapay, Klara; Burley, Stephen K. Proteins: Structure, Function, and Genetics, Vol. 10, Issue 4 https://doi.org/10.1002/prot.340100407	journal	April 1991
Diffuse X-Ray Scattering to Model Protein Motions Wall, Michael E.; Adams, Paul D.; Fraser, James S. Structure, Vol. 22, Issue 2 https://doi.org/10.1016/j.str.2014.01.002	journal	February 2014
Automated identification of functional dynamic contact networks from X-ray crystallography van den Bedem, Henry; Bhabha, Gira; Yang, Kun Nature Methods, Vol. 10, Issue 9 https://doi.org/10.1038/nmeth.2592	journal	August 2013
On the Relationship between Diffraction Patterns and Motions in Macromolecular Crystals Moore, Peter B. Structure, Vol. 17, Issue 10 https://doi.org/10.1016/j.str.2009.08.015	journal	October 2009
The Protein Data Bank Berman, H. M. Nucleic Acids Research, Vol. 28, Issue 1 https://doi.org/10.1093/nar/28.1.235	journal	January 2000
Accessing protein conformational ensembles using room-temperature X-ray crystallography Fraser, J. S.; van den Bedem, H.; Samelson, A. J. Proceedings of the National Academy of Sciences, Vol. 108, Issue 39 https://doi.org/10.1073/pnas.1111325108	journal	September 2011
Correlated Dynamics Determining X-Ray Diffuse Scattering from a Crystalline Protein Revealed by Molecular Dynamics Simulation Meinhold, Lars; Smith, Jeremy C. Physical Review Letters, Vol. 95, Issue 21 https://doi.org/10.1103/PhysRevLett.95.218103	journal	November 2005
Parallel replica method for dynamics of infrequent events Voter, Arthur F. Physical Review B, Vol. 57, Issue 22 https://doi.org/10.1103/PhysRevB.57.R13985	journal	June 1998
A sampling problem in molecular dynamics simulations of macromolecules. Clarage, J. B.; Romo, T.; Andrews, B. K. Proceedings of the National Academy of Sciences, Vol. 92, Issue 8 https://doi.org/10.1073/pnas.92.8.3288	journal	April 1995

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