Observation of multiple folding pathways of beta-hairpin trpzip2 from independent continuous folding trajectories.

Abstract

After 10-year investigations, the folding mechanisms of beta-hairpins are still under debate. Experiments strongly support zip-out pathway, while most simulations prefer the hydrophobic collapse model (including middle-out and zip-in pathways). In this article, we show that all pathways can occur during the folding of beta-hairpins but with different probabilities. The zip-out pathway is the most probable one. This is in agreement with the experimental results. We came to our conclusions by 38 100-ns room-temperature all-atom molecular dynamics simulations of the beta-hairpin trpzip2. Our results may help to clarify the inconsistencies in the current pictures of beta-hairpin folding mechanisms.