The first class aims to model the residence time via an empirical correlation between the simulated unbinding time and the experimental residence time, however, it relies on the assumption that the observed dynamics are realistic and that the kinetics are driven exclusively by the motion of the ligand. Examples of this class of methods include Random Acceleration MD and Scaled MD. In these techniques, the empirical calibration of a series-specific regression model is paramount. Therefore a significant upfront experimental effort and computational benchmarking of various parameters is required before they can be employed prospectively in an active drug discovery program. As such, when they fail, it may be difficult to understand the reasons and systematically improve them.