  We investigate the folding mechanism of the WW domain Fip35 using a realistic
atomistic force field by applying the Dominant Reaction Pathways (DRP)
approach. We find evidence for the existence of two folding pathways, which
differ by the order of formation of the two hairpins. This result is consistent
with the analysis of the experimental data on the folding kinetics of WW
domains and with the results obtained from large-scale molecular dynamics (MD)
simulations of this system. Free-energy calculations performed in two
coarse-grained models support the robustness of our results and suggest that
the qualitative structure of the dominant paths are mostly shaped by the native
interactions. Computing a folding trajectory in atomistic detail only required
about one hour on 48 CPU's. The gain in computational efficiency opens the door
to a systematic investigation of the folding pathways of a large number of
globular proteins.
