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

  title={Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution.},
  author={Yong Duan and Peter A. Kollman},
  volume={282 5389},
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, about two orders of magnitude longer than the longest simulation of a protein in water reported to date. Starting with an unfolded state of villin headpiece subdomain, hydrophobic collapse and helix formation occur in an initial phase, followed by conformational readjustments. A marginally stable… 

Parallel tempering molecular dynamics folding simulation of a signal peptide in explicit water

Parallel temperature molecular dynamics simulations are used to explore the folding of a signal peptide, a short but functionally independent domain at the N‐terminus of proteins, and the major group of obtained structures matches the NMR structure very closely.

Accelerated simulation of unfolding and refolding of a large single chain globular protein

Novel strategies for contracting simulation times in protein dynamics that enable us to study a complex protein with molecular weight in excess of 34 kDa and throw new light on the protein-folding process are developed.

Quasiequilibrium unfolding thermodynamics of a small protein studied by molecular dynamics simulation with an explicit water model.

The calculated unfolding quasiequilibrium thermodynamics of G-IgG-binding domain B1 (GB1) shows the experimentally observed protein transitions, which agree with the recent experiment result in which GB1 has more than one intermediate.

Computational protein folding: From lattice to all-atom

A recent microsecond-length molecular dynamics simulation on a small protein, villin headpiece subdomain, with an explict atomic-level representation of both protein and solvent, has marked the beginning of direct and realistic simulations of the folding processes.

Two-state folding over a weak free-energy barrier.

Computer simulations of membrane protein folding: structure and dynamics.

Direct folding simulation of a long helix in explicit water

A recently proposed Polarizable Hydrogen Bond (PHB) method has been employed to simulate the folding of a 53 amino acid helix (PDB ID 2KHK) in explicit water. Under PHB simulation, starting from 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.

Molecular Dynamics Simulations to Study Protein Folding and Unfolding

Even if one could use a computer 100 times faster than the currently fastest processor to eliminate the time scale problem, most proteins would not fold to the native structure because of the large systematic error and the marginal stability of the folded state typically ranging from 5 to 15 kcal mol .



A model of the molten globule state from molecular dynamics simulations.

  • V. DaggettM. Levitt
  • Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1992
The results of molecular dynamics simulations of the unfolding of reduced bovine pancreatic trypsin inhibitor are presented, providing an in-depth view of this state and details of water-protein interactions that cannot yet be obtained experimentally.

"New view" of protein folding reconciled with the old through multiple unfolding simulations.

A synthesis of the "new" and the classical view of protein folding with a preferred pathway on a funnel-like average energy surface is suggested.

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.

Direct observation of fast protein folding: the initial collapse of apomyoglobin.

Experiments on mutants and consideration of steady-state CD and fluorescence spectra indicate that the observed microsecond phase monitors assembly of an A x (H x G) helix subunit in the protein-folding history.

Simulations of the Folding of a Globular Protein

Dynamic Monte Carlo simulations of the folding of a globular protein, apoplastocyanin, have been undertaken in the context of a new lattice model of proteins that includes both side chains and

Molecular dynamics simulations of the unfolding of apomyoglobin in water.

Detailed analyses of the final structures and the unfolding pathways at high temperature clearly show that the most stable alpha-helical regions are those in contact with other helices.

Diffusion-limited contact formation in unfolded cytochrome c: estimating the maximum rate of protein folding.

N nanosecond-resolved spectroscopy shows that under strongly denaturing conditions, regions of unfolded cytochrome separated by approximately 50 residues diffuse together in 35-40 microseconds, which leads to an estimate of approximately (1 microsecond)-1 as the upper limit for the rate of protein folding.

Molecular dynamics simulations of protein unfolding and limited refolding: characterization of partially unfolded states of ubiquitin in 60% methanol and in water.

The results and interpretations using the different experimental techniques can be reconciled by a single state, bringing into question the practice of interpreting protection to hydrogen exchange in terms of native secondary and tertiary structure, especially when one has weak patterns and low protection factors.

Structures of folding intermediates.

  • O. Ptitsyn
  • Chemistry
    Current opinion in structural biology
  • 1995