Molecular dynamics simulation of nonsteroidal antiinflammatory drugs, naproxen and relafen, in a lipid bilayer membrane

Naproxen and relafen, as nonsteroidal antiinflammatory drugs, were simulated in neutral and charged forms and their effects on a lipid bilayer membrane were investigated by molecular dynamics simulation using Groningen machine for chemical simulations software (GROMACS). Simulation of 10 systems was performed, which included different dosages of the drug molecules, naproxen and Relafen, in charged and neutral forms, and a mixture of naproxen and Relafen in neutral forms. The effects of the mixture and the individual drugs' dosages on membrane properties, such as electrostatic potential, order parameter, diffusion coefficients, and hydrogen bond formation, were analyzed. Hydration of the drugs in the membrane system was investigated using radial distribution function analysis. Using fully hydrated dimyristoylphosphatidylcholine (DMPC) as a reference system, 128 lipid molecules and water molecules were simulated exclusively, and the same simulation technique was performed on 10 other systems, including drug mixtures and a DMPC membrane. Angular distributions of lipid chains of the membrane were calculated, and the effects of the drug insertion and chain orientation in the membrane were evaluated. © 2013 Wiley Periodicals, Inc. Nonsteoridal antiinflammatory drugs, such as naproxen and relafen, are commonly prescribed in a variety of pathologies. This article studies relafen and its mixture with naproxen, which is compared to naproxen in charged and neutral forms. The effect of level of these drugs' dosage on their diffusion coefficients, electrostatic potentials, hydrogen bond formations, order parameters, mass densities, and radial distribution functions are studied. It is found that a maximal diffusion coefficient must exist at some intermediate levels of dosage.