Fig. 1.

Partial unfolding during function, known as cracking (2), was predicted to be a general property that allows proteins to reduce free-energy barriers and accelerate functional kinetics. In EGFR kinase, crystal structures of the active (Left) and inactive (Right) forms might suggest that interconversion can be fully described by simple displacements/rotations. Through the use of many-microsecond molecular dynamics simulations, Shan et al. (6) has directly observed specific residues (circled) partially unfolding and refolding during this transition.