After the optimization of charges, dihedral potential energy functions were fit based on QM energy scans. The dihedrals suggested for optimization by CGenFF penalty scores were all linked through the ring of sorgoleone and dihydrosorgoleone (Figures and). These dihedrals are naturally coupled together, and are fit through a collective set of QM energy scans. In the case of sorgoleone, the CGenFF parameter overestimates the barrier around the energy minima in the scan (Figure ). By contrast, the initial CGenFF parameters for hydroxysorgoleone underestimated the barrier heights (Figure ). After optimization, the discrepancy between the energy scans was significantly reduced, representing an accurate model for these crucial compounds. Permeation for Sorgoleone and its Precursor into Sorghum Membrane