Dissociation Rate Calculation via Constant-force Steered Molecular Dynamics Simulation

Steered molecular dynamics (SMD) simulations have been applied to molecular dissociation events by adding a harmonic force to molecules. Further, molecules are pulled at a constant velocity. However, instead of the constant-velocity pulling, we use a constant force: the constant-force SMD (CF-SMD) simulation. The CF-SMD simulation employs a constant force to reduce the activation barrier of molecular dissociation, thereby enhancing the dissociation event. Here, we present the capability of the CF-SMD simulation to estimate the dissociation rate at equilibrium. We performed all-atom CF-SMD simulations for NaCl and protein–ligand systems, producing dissociation rates at various forces. We extrapolated these values to the dissociation rate without a constant force using the Dudko–Hummer–Szabo model. We demonstrate that the CF-SMD simulations and the model predicted the dissociation rate in equilibrium. A CF-SMD simulation is a powerful tool for estimating the dissociation rate in a direct and computationally efficient manner.