Atomic-Level Characterization of the Structural Dynamics of Proteins

@article{Shaw2010AtomicLevelCO,
  title={Atomic-Level Characterization of the Structural Dynamics of Proteins},
  author={David E. Shaw and Paul Maragakis and Kresten Lindorff-Larsen and Stefano Piana and Ron O. Dror and Michael P. Eastwood and Joseph A. Bank and John M. Jumper and John K. Salmon and Yibing Shan and Willy Wriggers},
  journal={Science},
  year={2010},
  volume={330},
  pages={341 - 346}
}
Following Folding Fast Many protein functions involve conformational changes that occur on time-scales between tens of microseconds and milliseconds. This has limited the usefulness of all-atom molecular dynamics simulations, which are performed over shorter time-scales. Shaw et al. (p. 341) now report millisecond-scale, all-atom molecular dynamics simulations in an explicitly represented solvent environment. Simulation of the folding of a WW domain showed a well-defined folding pathway and… 
Interaction Networks in Protein Folding via Atomic-Resolution Experiments and Long-Time-Scale Molecular Dynamics Simulations
TLDR
The integration of atomic-resolution experimental and computational methods offers the potential for elucidating key aspects of protein folding that are not revealed by either approach alone, and the methods employed in this study are likely to prove broadly applicable to the fine analysis of folding mechanisms in fast folding proteins.
Atomistic description of the folding of a dimeric protein.
TLDR
It is found that the isolated monomer is unstable but that, early in the folding pathway, nascent native structure is stabilized by contacts between the two monomer subunits, as in an induced-folding model.
Atomic-level description of ubiquitin folding
TLDR
The findings related to the folding of ubiquitin are consistent, for the most part, with the folding principles derived from the simulation of fast-folding proteins, suggesting that these principles may be applicable to a wider range of proteins.
Structural Characterization of λ-Repressor Folding from All-Atom Molecular Dynamics Simulations.
TLDR
The five-helix bundle λ-repressor fragment is observed to fold into a native-like topology at intermediate temperature and a slow-folding pathway was identified and the simulations suggest new experimental observables for better monitoring the folding process.
Protein folding and macromolecular dynamics: Fundamental limits of length and time scales
In this thesis, physics-based models of protein folding at the secondary and tertiary level are developed to resolve long-standing issues of protein folding kinetics. As discussed in the
Sampling of the conformational landscape of small proteins with Monte Carlo methods
TLDR
An all-atom Monte Carlo approach is reported that permits the modelling of the large-scale conformational change of proteins using standard off-the-shelf computational hardware and standard all- atom force fields and discusses limitations that still remain.
Native contacts determine protein folding mechanisms in atomistic simulations
TLDR
This work uses recently published microsecond to millisecond all-atom molecular dynamics simulations of proteins folding and unfolding to show, remarkably, that nonnative contacts are irrelevant to the mechanism of folding in most cases.
Native structure-based modeling and simulation of biomolecular systems per mouse click
TLDR
This work establishes an efficient infrastructure for native structure-based models to support the community and enable high-throughput simulations on remote computing resources via GridBeans and UNICORE middleware and demonstrates the power of this approach for protein folding simulations for a range of proteins.
Protein folding kinetics and thermodynamics from atomistic simulation
TLDR
This work showcases how computer simulation has now developed into a mature tool for the quantitative computational study of protein folding and dynamics that can provide a valuable complement to experimental techniques.
...
...

References

SHOWING 1-10 OF 154 REFERENCES
Ten-microsecond molecular dynamics simulation of a fast-folding WW domain.
TLDR
A ten-microsecond simulation of an incipient downhill-folding WW domain mutant along with measurement of a molecular time and activated folding time of 1.5 microseconds and 13.3 microseconds is reported.
Microsecond molecular dynamics simulation shows effect of slow loop dynamics on backbone amide order parameters of proteins.
TLDR
Results from a 1.2 micros explicit solvent MD simulation of the protein ubiquitin are compared with previously determined backbone order parameters derived from NMR relaxation experiments, revealing fluctuations in three loop regions that occur on time scales comparable to or longer than that of the overall rotational diffusion of ubiquitIn.
Phi-value analysis by molecular dynamics simulations of reversible folding.
TLDR
The interpretation of Phi values based on the ratio of atomic contacts at the TS over the native state is in agreement with the TS structures of wild-type peptide, however, Phi values tend to overestimate the nativeness of the TS ensemble, when interpreted neglecting the nonnative interactions.
Protein conformational transitions: the closure mechanism of a kinase explored by atomistic simulations.
TLDR
Simulations of the atomistic dynamics of the "open-to-closed" movement of the cyclin-dependent kinase 5 (CDK5) have been simulated and a new sampling method turned out to be well-suited for investigating at an atomistic level the energetics and dynamics of kinase large-scale conformational motions.
Absolute comparison of simulated and experimental protein-folding dynamics
TLDR
This work has used a distributed computing implementation to produce tens of thousands of 5–20-ns trajectories to simulate mutants of the designed mini-protein BBA5 and the fast relaxation dynamics these predict were compared with the results of laser temperature-jump experiments.
Nanosecond to microsecond protein dynamics probed by magnetic relaxation dispersion of buried water molecules.
TLDR
This new NMR method is introduced and validated by presenting and analyzing an extensive set of 2H and 17O MRD data from cross-linked gels of two model proteins and determines residence times and order parameters of four internal water molecules in these proteins and shows that they are quantitatively consistent with the information available from crystallography and solution MRD.
Simultaneous determination of protein structure and dynamics
TLDR
The procedure combines the strengths of nuclear magnetic resonance spectroscopy—for obtaining experimental information at the atomic level about the structural and dynamical features of proteins—with the ability of molecular dynamics simulations to explore a wide range of protein conformations.
...
...