Measuring passive permeability of sorgoleone and its precursors through a sorghum plasma membrane model is carried out systematically through a MD simulation campaign. The methodological starting point was the optimization of molecular parameters for sorgoleone and its precursors. Optimized parameters enable us to use these molecules to predict their localization in a membranous environment through microsecond-scale unbiased MD simulation. However, since sampling from classical MD simulation is limited to local free-energy minima and does not explore the entire energy landscape, we also use REUS techniques to estimate the permeability coefficient.