How the diffusivity profile reduces the arbitrariness of protein folding free energies

Journal of Chemical Physics - Tập 132 Số 24 - 2010
Michael Hinczewski1,2, Yann von Hansen1, Joachim Dzubiella1, Roland R. Netz1
1Technical University of Munich 1 Department of Physics, , 85748 Garching, Germany
2University of Maryland 2 Institute for Physical Science and Technology, , College Park, Maryland 20742, USA

Tóm tắt

The concept of a protein diffusing in its free-energy folding landscape has been fruitful for both theory and experiment. Yet the choice of the reaction coordinate (RC) introduces an undesirable degree of arbitrariness into the problem. We analyze extensive simulation data of an α-helix in explicit water solvent as it stochastically folds and unfolds. The free-energy profiles for different RCs exhibit significant variations, some having an activation barrier, while others not. We show that this variation has little effect on the predicted folding kinetics if the diffusivity profiles are properly taken into account. This kinetic quasi-universality is rationalized by an RC rescaling, which, due to the reparameterization invariance of the Fokker–Planck equation, allows the combination of free-energy and diffusivity effects into a single function, the rescaled free-energy profile. This rescaled free energy indeed shows less variation among different RCs than the bare free energy and diffusivity profiles separately do, if we properly distinguish between RCs that contain knowledge of the native state and those that are purely geometric in nature. Our method for extracting diffusivity profiles is easily applied to experimental single molecule time series data and might help to reconcile conflicts that arise when comparing results from different experimental probes for the same protein.

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Journal of Chemical Physics

Tập 132 Số 24

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