Insight Into the Molecular Dynamic Simulation Studies of Reactive Oxygen Species in Native Skin Membrane

In recent years, the role of reactive oxygen species (ROS) in regulating cancer cell apoptosis, inflammation, cell ischemia, and cell signalling pathways has been well established. The most common sources of intracellular ROS are the mitochondrial electron transport system, NADH oxidase, and cytochrome P450. In this study, we investigated the dynamics and permeability of ROS using molecular dynamics simulations on native skin-lipid bilayer membranes. Native skin-lipid bilayersarecomposed of ceramide, cholesterol, and free fatty acid in analmost equal molar ratio (1:1:1). Dynamic distribution studiesonROS, i.e. H2O2 and O2 (1O2 by analogy),revealed that these species interact with cholesterol as a primary target in lipidperoxidation of theskin-lipid bilayer. Moreover, the permeability of ROS, i.e. H2O2, HO, HOO, and O2, along the skin-lipid bilayer was measured using free energy profiles (FEPs). TheFEPsshowed that in spite of high-energy barriers, ROStraveledthrough the membrane easily.Breaching the free energy barriers, these ROS permeated into the membrane, inflicting oxidative stress and causingapoptosis.Collectively, the insight acquired from simulations may resultin a better understanding of oxidative stress at the atomic level.