Ultrafast and downhill protein folding

Ultrafast folding proteins have served an important role in benchmarking molecular dynamics simulations and testing protein folding theories. These proteins are simple enough and fold fast enough that realistic simulations are possible, which facilitates the direct comparison of absolute folding rates and folding mechanisms with those observed experimentally. Such comparisons have achieved remarkable success, but have also revealed the shortcomings that remain in experiment, theory and simulation alike. Some ultrafast folding proteins may fold without encountering an activation barrier (downhill folding), allowing the exploration of the molecular timescale of folding and the roughness of the energy landscape. The biological significance of ultrafast folding remains uncertain, but its practical significance is crucial to progress in understanding how proteins fold.