Protein folding kinetics and thermodynamics from atomistic simulations

• Determining protein folding kinetics and thermodynamics from all-atom molecular dynamics (MD) simulations without using experimental data represents a formidable scientific challenge because simulations can easily get trapped in local minima on rough free energy landscapes. This necessitates the computation of multiple simulation trajectories, which can be independent from each other or coupled in some manner, as, for example, in the replica exchange MD method. Here we present results obtained with a new analysis tool that allows the deduction of faithful kinetics data from a heterogeneous ensemble of simulation trajectories. The method is demonstrated on the decapeptide Chignolin for which we predict folding and unfolding time constants of 1.0±0.3 and 2.6±0.4  μs, respectively. We also derive the energetics of folding, and calculate a realistic melting curve for Chignolin.

Ämnesord

NATURVETENSKAP  -- Biologi -- Bioinformatik och systembiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)

Nyckelord

Computer Simulation

Kinetics

Models; Chemical

Models; Molecular

Protein Folding

Proteins/*chemistry/*ultrastructure

Quantum Theory

Research Support; Non-U.S. Gov't

Thermodynamics

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)