dcTMD – is a method for computation of kinetic rates based on dissipation-corrected targeted molecular dynamics simulations combined with temperature-boosted Langevin sampling.

Dissipation corrected targeted MD (dcTMD) is MD-based approach where an external pulling force is applied to the ligand along a reaction coordinate via a moving distance constraint. The system evolution is described by a memory-free Langevin equation. Sampling multiple dcTMD trajectories combined with Jarzynski’s equality, enables estimation of both the free energy profile of ligand dissociation and the friction field along the dissociation coordinate. These quantities are then used to describe the unbiased motion of the system with the Langevin equation and thus to obtain absolute values of kinetic (binding and unbinding) rates. A speed-up in simulations is gained because (1) the equation is solved for only one (reaction) coordinate, and (2) a high temperature is employed to ensure that multiple unbinding events are observed.

Example Cases

For examples of previously performed studies in which dcTMD with T-boosted Langevin Simulations was the primary method used, see the following example cases: