Folding mechanism of all-beta globular proteins.

Elucidating the mechanism for the fast folding of proteins is a challenging task. In our earlier work, we introduced the concept of "long-range order" and related it successfully to protein folding rates. In this article, we propose a new hypothesis for the folding of two-state all-beta proteins. The mechanism is based on the formation of a hydrophobic core, propagation of beta-strands, and the establishment of hydrogen bonds. Our hypothesis has been strengthened by the observation of a folding nucleus in beta-strands and the hydrogen-bonding network between residues in beta-strands. Our insights on protein folding show an excellent agreement with experimental observations.