Protein folding as an evolutionary process

Department of Biosciences, University of Helsinki, Finland
Physica A: Statistical Mechanics and its Applications (Impact Factor: 1.73). 03/2009; 388(6):851-862. DOI: 10.1016/j.physa.2008.12.004


Protein folding is often depicted as a motion along descending paths on a free energy landscape that results in a concurrent decrease in the conformational entropy of the polypeptide chain. However, to provide a description that is consistent with other natural processes, protein folding is formulated from the principle of increasing entropy. It then becomes evident that protein folding is an evolutionary process among many others. During the course of folding protein structural hierarchy builds up in succession by diminishing energy density gradients in the quest for a stationary state determined by surrounding density-in-energy. Evolution toward more probable states, eventually attaining the stationary state, naturally selects steeply ascending paths on the entropy landscape that correspond to steeply descending paths on the free energy landscape. The dissipative motion of the non-Euclidian manifold is non-deterministic by its nature which clarifies why it is so difficult to predict protein folding.

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