Comparison between the empirical cumulative distribution function (CDF) of morphine residence times derived from infrequent metadynamics simulations and the CDF of residence times derived from a theoretical model. [(a)–(c)] Results from infrequent metadynamics simulation runs with bias deposition intervals of 20 ps, 30 ps, and 50 ps respectively. The p-values for each fit derived from the KS test are also shown. (d) Range of morphine residence times, τ, calculated from the same simulations. Residence times are in unit of minutes, while bias deposition intervals are in picoseconds.