Dissociation Rate Calculation via Constant-Force Steered Molecular Dynamics Simulation

Steered molecular dynamics (SMD) simulations are used to study molecular dissociation events by applying a harmonic force to the molecules and pulling them at a constant velocity. Instead of 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 time at equilibrium. We performed all-atom CF-SMD simulations for NaCl and protein–ligand systems, producing dissociation time at various forces. We extrapolated these values to the dissociation rate without a constant force using Bell's model or the Dudko–Hummer–Szabo model. We demonstrate that the CF-SMD simulations with the models predicted the dissociation time in equilibrium. A CF-SMD simulation is a powerful tool for estimating the dissociation rate in a direct and computationally efficient manner.