This split reaction coordinate is analogous to simulations performed for fatty acid permeation, and eliminates ambiguities that might arise from two orientations or conformations for a molecule sharing a center of mass (Figure ). These REUS calculation are for sorgoleone desorption from membrane to absorption in water (A), leaflet exchange of sorgoleone within a membrane (B) and sorgoleone desorption from membrane to absorption in an organic phase phase of sorgoleone (C). Each representation is detailing the relative positioning of the sorgoleone (yellow) compared with the membrane (atomically colored spheres), water (blue), and the organic phase of sorgoleone (green).