Absolute comparison of simulated and experimental protein-folding dynamics

  title={Absolute comparison of simulated and experimental protein-folding dynamics},
  author={Christopher D. Snow and Houbi Nguyen and Vijay S. Pande and Martin Gruebele},
Protein folding is difficult to simulate with classical molecular dynamics. Secondary structure motifs such as α-helices and β-hairpins can form in 0.1–10 µs (ref. 1), whereas small proteins have been shown to fold completely in tens of microseconds. The longest folding simulation to date is a single 1-µs simulation of the villin headpiece; however, such single runs may miss many features of the folding process as it is a heterogeneous reaction involving an ensemble of transition states. Here… 

Folding Kinetics and Unfolded State Dynamics of the GB1 Hairpin from Molecular Simulation.

The C-terminal β-hairpin of protein G is a 16-residue peptide that folds in a two-state fashion akin to many larger proteins. However, with an experimental folding time of ∼6 μs, it remains a

Ten-microsecond molecular dynamics simulation of a fast-folding WW domain.

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.

Microscopic events in β-hairpin folding from alternative unfolded ensembles

The first unbiased folding simulations of the GB1 hairpin in explicit solvent are performed, using hundreds of microsecond-long molecular dynamics simulations, and it is found that the mechanism of the hairpin folding is insensitive to the details of the initial unfolded ensemble.

Dynamics, energetics, and structure in protein folding.

Recent developments in protein folding are discussed, emphasizing aspects that can serve as a guide for experimentalists interested in exploiting this new avenue of research.

Does water play a structural role in the folding of small nucleic acids?

It is found that hydrophobic collapse follows a predominantly expulsive mechanism in which a diffusion-search of early structural compaction is followed by the final formation of native structure that occurs in tandem with solvent evacuation, indicating the formation of the secondary structure appears to be more rapid than the fastest ionic degrees of freedom.

Ultrafast folding of α3D: A de novo designed three-helix bundle protein

The folding/unfolding kinetics of α3D, a small designed three-helix bundle, are described, revealing a single-exponential process consistent with a minimal folding time and indicating that a protein can fold on the 1- to 5-μs time scale.

How fast fast-folding proteins fold in silico.

  • Y. Pang
  • Biology
    Biochemical and biophysical research communications
  • 2017



Thermodynamics and Kinetics of Folding of Two Model Peptides Investigated by Molecular Dynamics Simulations

The folding of an R-helix and a ‚-hairpin was studied by 862 molecular dynamics simulations with an implicit solvation model that allowed sampling of a total of 4 Is. The average effective energy is

Folding simulations of a three-stranded antiparallel β-sheet peptide

Protein folding is a grand challenge of the postgenomic era. In this paper, 58 folding events sampled during 47 molecular dynamics trajectories for a total simulation time of more than 4 μs provide

Beta-hairpin folding simulations in atomistic detail using an implicit solvent model.

The results are consistent with a three-state mechanism with a single rate-limiting step in which a varying final hydrogen bond pattern is apparent, and semi-helical off-pathway intermediates may appear early in the folding process.

β-hairpin folding simulations in atomistic detail using an implicit solvent model1

Abstract We have used distributed computing techniques and a supercluster of thousands of computer processors to study folding of the C-terminal β-hairpin from protein G in atomistic detail using the

Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution.

An implementation of classical molecular dynamics on parallel computers of increased efficiency has enabled a simulation of protein folding with explicit representation of water for 1 microsecond,

Protein folding and unfolding in microseconds to nanoseconds by experiment and simulation.

Preliminary simulations did indeed conform to unfolding on this time scale, and similar transition states were observed in simulations at 100 degrees C and 225 degrees C, suggesting that high-temperature simulations provide results applicable to lower temperatures.

From folding theories to folding proteins: a review and assessment of simulation studies of protein folding and unfolding.

Assessment of the two methods suggests that both can provide, often complementary, details of folding mechanism and thermodynamics, but this success relies on adequate sampling of diverse conformational regions for the biased-sampling free energy approach and many trajectories at multiple temperatures for unfolding studies.

Reversible peptide folding in solution by molecular dynamics simulation.

Long-standing questions on how peptides fold are addressed by the simulation at different temperatures of the reversible folding of a peptide in solution in atomic detail, implying that the search problem in peptide (or even protein) folding is surmountable using dynamics simulations.

Navigating the folding routes

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Fast events in protein folding: relaxation dynamics of secondary and tertiary structure in native apomyoglobin.

Helix formation precedes the formation of tertiary structure by over three orders of magnitude in this protein, and the distinct thermodynamics and kinetics observed for the apomyoglobin substructures suggest that they fold independently, or quasi-independently.