Origin of Protein Quake: Energy Waves Conducted by a Precise Mechanical Machine

A long-standing challenge in protein biophysics is to understand protein quake in myoglobin─the structural dynamics responsible for redistributing the excess heme energy after photolysis. Despite extensive efforts, the molecular mechanism of this process remains elusive. Using the energy flow theory, we uncovered a fundamental new phenomenon: the heme energy is redistributed by sinusoidal waves with a ubiquitous fundamental frequency and two overtones. The energy waves emanate from the heme into the myoglobin backbone via a conduit of five consecutive dihedrals of the proximal histidine and then travel quickly along the backbone to reach sidechains across the protein. This mechanism is far more effective than the diffusion-based mechanism from previous studies because waves are systematic while diffusion is random. To propagate energy waves, coordinates must cooperate, resulting in collective modes that are singular vectors of the generalized work functional. These modes show task partitioning: a handful of high-energy modes generate large-scale breathing motion, which loosens up the protein matrix to enable hundreds of low-energy vibrational modes for energy transduction.