The project currently focuses on modelling the mucus layer in the olfactory region, as this is the first barrier for intranasal drug transport. This mucus layer consists of Mucin molecules which are major limiting factors for drug transport. The image from the VMD software shows all atom molecular model of MUC-5AC mucin, represented as ribbons and Memantine in VDW representation. PDB files for these molecules were obtained from Protein Data Bank and simulated using AmberGS force field on GROMACS, an open-source efficient MD code. During MD analysis, the system was minimised to provide a minimal energy configuration using steepest descent technique. This minimised system was further equilibrated using NVT and NPT thermodynamic state ensembles. The NVT thermal equilibration was done with a positional restraint on all the atoms and a modified Berendsen thermostat. Subsequently, NPT pressure equilibration was applied with the same thermostat in addition to the Parrinello−Rahmen pressure coupling. This temperature and pressure equilibrated system of MUC-5AC and Memantine was then used as the initial configuration for the MD simulation. During dynamic analysis, atoms did not have any positional restraints and were free to move in their most energetically favorable positions. This simulation was conducted using a 2 fs time step for 20,000 steps, giving a simulation time of 40 ps. Further simulations will be performed on proffesional GPUs allowing simulation of larger time scales. After analysing all the important Mucin molecules, appropriate Coarse graining technique will be chosen to perform Dynamic simulations on the coarse grained molecules.
