Development and application of coarse-grained MARTINI model of skin lipid ceramide [AP].

Stratum corneum (SC), the outermost layer of the skin, contains large variety of lipids, endowing them with the amphiphilic properties, needed to fulfil their key role in skin's barrier function. The individual role of lipid types in the barrier function is difficult to understand due to the immense heterogeneity and complexity of the lipid's organization within the SC. The lipid organization is being explored using both computational (molecular dynamics simulations) and experimental (neutron diffraction) techniques. Even though atomistic simulations provide unprecedented atomic level details, the major limitation is time and length scale that can be achieved with decent computational facility. Alternatively, coarse-grain (CG) models are currently being used to capture physics at bigger time and length scale without losing essential underlined structural information. In this study, a CG model of α-hydroxy phytosphingosines (CER[AP]) is developed based on philosophy of MARTINI force field. At first, the model is validated with various atomistic simulations and available experimental data. Later on, the model's compatibility with other major skin lipids, cholesterol, and free fatty acid (palmitic acid) is checked by simulating a mixture of lipid multilayer in presence and absence of water. The developed model of CER[AP] is able to predict key structural properties within the acceptable error limits. The phenomena of ceramide conformation transformation, cholesterol flip-flop, and specificity of lipid arrangement within the multilayered systems is observed during the simulation. This signifies the importance of model in capturing higher order structural transformations.