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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    • "Using a set of 29 unrelated proteins, Chen demonstrated that the average prediction result from their method is significantly better than predictions based on other computation methods. Sharma et al. [13] provided a description which is consistent with other natural processes, that the protein folding is formulated from the principle of increasing entropy. It then became evident that protein folding is an evolutionary process among many others. "
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    • "The non-computability manifests itself when searching for the optimal alignment of one particular segment, because a positioning will affect the already adopted alignments of other segments. That is, the computational problem keeps changing when it is being solved [31], which is familiar from many other hard problems [32] such as protein folding [33]. Therefore, the calculated lineages, ranked in terms of probabilities, depend on the particular set of aligned sequences, and no alignment can be announced as the actual. "
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    • "Thus, when a quantum is absorbed from a common reservoir of potential energy by one process, the same quantum cannot also be taken up by another. Despite the non-deterministic character of natural processes [41] [42] [43] [44], the least-time quest to consume free energy will have been directing the courses of energy flows so as to result in the rules and regularities that we see in nature [45] [46] [47] [48] [49]. The path-dependence of statistical processes can also be formulated as the statement that among all conceivable worlds the most probable must be the actual one [50], in the sense that Leibniz found the actual world to be the best of all possible ones. "
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