Protein folding kinetics: timescales, pathways and energy landscapes in terms of sequence-dependent properties.

  title={Protein folding kinetics: timescales, pathways and energy landscapes in terms of sequence-dependent properties.},
  author={T Veitshans and Dmitri K. Klimov and D. Thirumalai},
  journal={Folding \& design},
  volume={2 1},

Cell dynamics of folding in two-dimensional model proteins.

Can Theory Predict Two-State Protein Folding Rates? An Experimental Perspective

Reviewing theoretical models of protein folding kinetics in terms of their ability to qualitatively rationalize this most basic of experimental observations finds that the properties known to account for variations in the folding rates of simple on- and off-lattice computational models do not account for the vast range of two-state folding rates observed in the laboratory.

Molecular dynamics of folding of secondary structures in Go-type models of proteins

This work considers six different secondary structures of proteins and construct two types of Go-type off-lattice models: with the steric constraints and without, which are found to be better folders and to be more stable.

Toward a quantitative description of microscopic pathway heterogeneity in protein folding.

Predictive methodology reveals the presence of rich ensembles of folding mechanisms that are generally invisible in experiments, reconciles the contradictory observations from experiments and simulations and provides an experimentally consistent avenue to quantify folding heterogeneity.

Ultrafast folding kinetics of WW domains reveal how the amino acid sequence determines the speed limit to protein folding

The special properties of fast-folding proteins are exploited to experimentally resolve the folding rate prefactor and investigate how much it varies among structural homologs, and the results confirm long-standing theoretical predictions and bring into focus the ratePrefactor as an essential element for understanding the mechanisms of folding.

Improved theoretical description of protein folding kinetics from rotations in the phase space of relevant order parameters.

A method is introduced to construct a better approximation for the reaction coordinate for protein folding from known order parameters by introducing a rotation in the phase space of the order parameters Q and Qn that leads to a fivefold improvement in the estimate of the folding rate.

Fast‐folding protein kinetics, hidden intermediates, and the sequential stabilization model

This study finds that the present microscopic model is indeed consistent with HIs and transition states, but such states occur in parallel, rather than along the single pathway predicted by the sequential stabilization model.

The folding pathways and thermodynamics of semiflexible polymers.

A rich variety of folding products, such as rod-like bundles, hairpins, toroids, and a mixture of them, are observed in the complete diagram of states, and knotted structures with a significant population are found in a certain range of bending stiffness in thermal equilibrium.


It is shown that, under the simulation conditions when the native basin of attraction (NBA) is the most stable, there is an excellent correlation between folding times τF and the dimensionless parameter σT=(Tθ−TF)/T δ, where Tθ is the collapse temperature and TF is the folding transition temperature.

Intermediates and transition states in protein folding.

There appears to be a relationship between the diversity of structures in the denatured state ensemble and the extent to which the TSE is plastic, and the consequences of multiple routes and intermediates on the transition state ensemble (TSE) in folding.



Kinetics and thermodynamics of folding in model proteins.

  • C. CamachoD. Thirumalai
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1993
Monte Carlo simulations on a class of lattice models are used to probe the thermodynamics and kinetics of protein folding. We find two transition temperatures: one at T theta, when chains collapse

Kinetics of protein folding: Nucleation mechanism, time scales, and pathways

The kinetics and thermodynamics of protein folding is investigated using low friction Langevin simulation of minimal continuum mode of proteins. We show that the model protein has two characteristic

Funnels, pathways, and the energy landscape of protein folding: A synthesis

The work unifies several previously proposed ideas concerning the mechanism protein folding and delimits the regions of validity of these ideas under different thermodynamic conditions.

Kinetics of protein folding. A lattice model study of the requirements for folding to the native state.

It is shown that successful folding does not require certain attributes that have been previously proposed as necessary for folding; these include a high number of short versus long-range contacts in the native state, a high content of the secondary structure in the original structure, a strong correlation between the native contact map and the interaction parameters, and the existence of aHigh number of low energy states with near-native conformation.

Principles of protein folding — A perspective from simple exact models

These studies suggest the possibility of creating “foldable” chain molecules other than proteins, and can account for the properties that characterize protein folding: two‐state cooperativity, secondary and tertiary structures, and multistage folding kinetics.

Kinetics of Folding of Proteins and RNA

Recent advances are described in the understanding of the kinetics of in vitro folding of globular proteins in terms of the underlying energy landscape as well as the requirements for RNA folding which are analogous to those of protein folding.

Optimization of rates of protein folding: the nucleation-condensation mechanism and its implications.

  • A. Fersht
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1995
The nucleation-condensation mechanism of CI2 fulfills the criteria for fast folding, and stable intermediates do form in the folding of more complex proteins, and this may be an unavoidable consequence of increasing size and nucleation at more than one site.

Transition states and folding dynamics of proteins and heteropolymers

We study the folding dynamics of short two‐dimensional self‐avoiding lattice model proteins and copolymers with specific HP sequences (H, hydrophobic, P, polar) that fold to unique native structures.

The nature of folded states of globular proteins

We suggest, using dynamical simulations of a simple heteropolymer modelling the α‐carbon sequence in a protein, that genetically the folded states of globular proteins correspond to statistically