Theory, simulations, and experiments show that proteins fold by multiple pathways

In PNAS (1), Englander and Mayne repeat an assertion, already made by them along with Bai and Sosnick in 1995 (2), that the modern energy landscape theory of protein folding, by emphasizing the parallelism of potential folding pathways, is incompatible with evidence that in some cases a single particular sequence of folding substructures dominates the set of folding trajectories. This assertion of the authors was false when made in 1995, and since then considerable collaborative work between the experimental and theoretical communities has made an irrefutable case against the notion that the only way proteins fold is by a single obligate pathway (ref. 3 and … [↵][1]1To whom correspondence may be addressed. Email: eaton{at}helix.nih.gov or pwolynes{at}rice.edu. [1]: #xref-corresp-1-1

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