Transient protein softening during the working cycle of a molecular machine

Proper functioning of proteins usually requires a certain internal flexibility provided by stochastic structural fluctuations on the picosecond time scale. In contrast with conventional steady-state experiments, we report on a novel type of (laser-neutron) pump-probe experiment combining in situ activation of protein function with a time-dependent test of protein dynamics using quasielastic neutron scattering. A transient protein softening is shown to occur during the photocycle of bacteriorhodopsin as a direct proof for the functional significance of protein flexibility.