REUS simulations were analyzed to determine both a free energy profile and a diffusivity profile for each molecule along both reaction coordinates to feed into Eq. 4. The free energy profiles were determined with a modified version of Bayesian Weighted Histogram Analysis Method (BayesWHAM), which uses Gibbs sampling of the known Dirichlet prior to rapidly assess uncertainty. Diffusion profile for Eq. 4 is calculated from variance and autocorrelation time of the biased motion along the reaction coordinate. The autocorrelation time itself is estimated from an exponential fit over the short time where a trajectory remains within a single umbrella. This approach is less sensitive to the harmonic restraint force than alternative calculation approaches, and is independent of momentum removal around restarts. To compute an overall permeability coefficient for the full process, we leverage the fact that the integral in Eq. 4 can be split into multiple components. The overall resistance to permeation is additive across the individual steps such as adsorption, leaflet exchange, and desorption in the total permeation process. This follows the prior precedents in other permeation studies for complex membranes or compounds. To create a connected free energy profile that spans the full space, we take advantage of our trajectories and free energies to reweight our sampling from one reaction coordinate to the other. From our free energy profiles, we can obtain a probability distribution in both distance space (P distance )