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David O'Neill


The stratum corneum is the topmost layer of the skin, which forms the main barrier to penetration of substances across the skin and to water loss from inside the body. It is believed that the lipid layers within the stratum corneum are the main contributors the skin's barrier properties. One of the major problems is that the organisation of the lipids into the lamellar layers remains poorly understood, due to the difficulty of high resolution imaging of the skin. Molecular simulation can help by zooming in on these structures at the molecular level but there are still multiple problems to overcome.

Computer simulations are a valuable technique for studying biological lipid membrane systems at the molecular level. Specifically, these simulations can be used to predict a range of structural, mechanical and dynamic properties various conditions. The majority of simulations in this field to date have focused on lipid membranes in the liquid-crystalline or fluid phase, typical of a cell membrane. However, a number of lipids, such as those found in skin, are found in the gel-phase at physiological temperatures. The problem with this for simulations is that in the gel-phase diffusion is slow and so effective sampling requires prohibitively long timescales. In practice, simulations of gel-phase lipids end up being highly dependent on the starting configuration. We are attempting to address this issue using a number of different methodologies including temperature and the use of soft-core potentials combined with Hamiltonian replica exchange molecular dynamics where we try to smooth the barriers in the free energy landscape leading to a more efficient equilibration. In this way the self-assembly, packing and other properties of the lipids can be investigated without prior knowledge of their starting configurations.


My research aims to solve skin lipid probelms by:CER2 bilayer


  • Investigating the effect of water concentration on the structural and mechanical properties of ceramide bilayers
  • Developing new simulation approaches to study mixtures of lipids in the gel phase. This will enable the self-assembly and packing of the skin lipids to be investigated without prior assumptions about the molecular arrangement
  • Simulating a range of ceramide and skin lipids to be investigated without prior assumptions about the molecular arrangement
  • Investigating the molecular transport of various compounds across the stratum corneum in the presence of additives
  • Using free energy calculations to predict the permeability coefficients of selected drug molecules
  • Ultimately, a more sophisticated model of the skin is the main aim, one that can be applied to predict skin transport and skin biophysics!
Recent Publications:

David William O'Neill, Sang Young Noh, and Rebecca Notman, Computational Pharmaceutics: Application of Molecular Modeling in Drug Delivery, Chapter 6 Computer Simulations of LIpid Membranes and Liposomes for Drug Delivery, Wiley 2015

Thind, R., O'Neill, D. W., Del Regno, A. and Notman, R. (2015) "Ethanol induces the formation of water-permeable defects in model bilayers of skin lipids" accepted to Chem. Comm. (Dec 2014)

If you have any questions or queries about my research feel free to email me at:

D dot O-Neill at warwick dot ac dot uk