Skin barrier simulation
The project aims at simulating drug diffusion through a model of the main barrier in human skin, the extracellular lipids in stratum corneum, as well as its formation using molecular dynamics (MD) simulations.
During the last period we have improved the accelerated weight histogram (AWH) method in GROMACS by enabling its use along alchemical free energy dimensions. This work has been done in collaboration with Berk Hess and Jack Lidmar. The manuscript is submitted, and under review, in Journal of Chemical Physics. This method is now used for combining one alchemical AWH dimension with another AWH pulling dimension in order to calculate the skin lipid barrier permeability more efficiently. The agreement to in vitro/ex vivo data is good in general. We have generated large amounts of data, with more in the pipeline, with the goal to publish these results in 2021. We will also study the effect of permeation enhancers more closely.
The Martini forcefield version 3 was not published until a month ago. This has delayed our efforts at trying to reproduce all-atom results in the coarse-grained forcefield. We hope to be able to focus more on this in the next period.