Cited 34 time in webofscience Cited 33 time in scopus

Benchmarking all-atom simulations using hydrogen exchange

Title
Benchmarking all-atom simulations using hydrogen exchange
Authors
Skinner, JJ[Skinner, John J.]Yu, W[Yu, Wookyung]Gichana, EK[Gichana, Elizabeth K.]Baxa, MC[Baxa, Michael C.]Hinshaw, JR[Hinshaw, James R.]Freed, KF[Freed, Karl F.]Sosnick, TR[Sosnick, Tobin R.]
DGIST Authors
Yu, W[Yu, Wookyung]
Issue Date
2014-11-11
Citation
Proceedings of the National Academy of Sciences of the United States of America, 111(45), 15975-15980
Type
Article
Article Type
Article
Keywords
Atomic ParticleChemistryDenatured StatesDeuterium Exchange MeasurementDeuterium Hydrogen ExchangeGTP-Binding ProteinsGuanine Nucleotide Binding ProteinHXHydrogenHydrogen BondHydrogen BondingHydrogen ExchangeMolecular DynamicsMolecular InteractionNuclear Magnetic ResonanceProteinProtein DenaturationProtein FoldingProtein Structure, TertiaryProtein Tertiary StructureProtein UnfoldingQuality ControlRecombinant ProteinRecombinant ProteinsUnfolded State
ISSN
0027-8424
Abstract
Long-time molecular dynamics (MD) simulations are now able to fold small proteins reversibly to their native structures [Lindorff-Larsen K, Piana S, Dror RO, Shaw DE (2011) Science 334(6055):517-520]. These results indicate that modern force fields can reproduce the energy surface near the native structure. To test how well the force fields recapitulate the other regions of the energy surface, MD trajectories for a variant of protein G are compared with data from site-resolved hydrogen exchange (HX) and other biophysical measurements. Because HX monitors the breaking of individual H-bonds, this experimental technique identifies the stability and H-bond content of excited states, thus enabling quantitative comparison with the simulations. Contrary to experimental findings of a cooperative, all-or-none unfolding process, the simulated denatured state ensemble, on average, is highly collapsed with some transient or persistent native 2° structure. The MD trajectories of this protein G variant and other small proteins exhibit excessive intramolecular H-bonding even for the most expanded conformations, suggesting that the force fields require improvements in describing H-bonding and backbone hydration. Moreover, these comparisons provide a general protocol for validating the ability of simulations to accurately capture rare structural fluctuations.
URI
http://hdl.handle.net/20.500.11750/2637
DOI
10.1073/pnas.1404213111
Publisher
National Academy of Sciences
Related Researcher
  • Author Yu, Woo Kyung Laboratory of Protein Biophysics
  • Research Interests protein biophysics; protein folding; protein dynamics and conformational change
Files:
There are no files associated with this item.
Collection:
Brain and Cognitive SciencesETC1. Journal Articles


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