Molecular simulation study on concentration effects of rofecoxib with POPC bilayer

The interactions between rofecoxib and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) bilayer were studied using all-atom molecular dynamics simulation method. Four POPC bilayer systems with different number of rofecoxib molecules were constructed to simulate different drug concentration. The free energy of rofecoxib passing across pure POPC bilayer has two minima (at z ∼1.2nm or 1.6nm). As for the high concentration model, the minimum of the free energy profile slightly shifts to the bilayer center. Moreover, the energy change from bulk water to POPC bilayer increases while the central barrier to cross the hydrophobic core of bilayer slightly decreases, suggesting that increasing drug concentration makes it favorable for rofecoxib to partition into the bilayer and easier to pass across bialyer center. Energy analysis show that the stabilization between the selected rofecoxib and other pre-inserted rofecoxib molecule is mainly due to van der Waals interaction energy. The predicted permeability of rofecoxib in high concentration model slightly weakens as compared with low concentration model.