Protein conformational fluctuations and free-energy transduction

Abstract

Non-equilibrium fluctuations, whether imposed externally or driven by an energy-releasing chemical reaction, can cause a protein to cycle through several conformations. This cycling can drive a process thermodynamically uphill even though any one conformation considered independently catalyzes the process in the downhill direction. This is because the different conformations have different rate constants (energy barriers) between the states in the catalytic cycle. Even though each conformation individually obeys detailed balance, the flashing between different energy profiles gives rise to a ratchet effect. Further, by exploiting protein conformational dynamics, a single stochastic input can be converted into two phase-shifted internal parameters (e.g. a kinetic barrier height and a binding well energy). This allows the output process to be driven nearly adiabatically, explaining in part the very high efficiencies observed for some biological energy-transduction processes. The results apply equally to driving a biochemical reaction away from equilibrium by an enzyme, to formation of an osmotic gradient across a membrane by a molecular pump, or to motion and generation of force by a molecular motor.