Investigation of benzodiazepines (BZDs) in a DPPC lipid bilayer: Insights from molecular dynamics simulation and DFT calculations.

Toxicity is an essential parameter for drug development process and drug design. In this context, the effects of concentration of two Benzodiazepine drugs (diazepam, clonazepam) on fully hydrated dipalmitoylphosphatidylcholine (DPPC) has been studied at 323 K using molecular dynamics simulations. Various properties of bilayer such as membrane area per lipid, mass density distributions, order parameters, radial distribution functions, lateral diffusion, and electrostatic potential have been examined at three different concentrations of each drug. The location of drugs in the membrane are estimated by free energy profiles and to evaluate the results at a more detailed theoretical level, density functional theory (DFT) calculations have been carried out. It was revealed that penetration into the bilayer for diazepam is more favorable than clonazepam. On the other hand, within the fatty acid tail area both drugs are located in the middle of membrane at ∼0.75-1.5 nm from center of bilayer.