Skin permeability prediction with MD simulation sampling spatial and alchemical reaction coordinates

Lidmar, Jack, 1968- (author): KTH,Tillämpad fysik,Kondenserade materiens teori

Hess, Berk (author): KTH,Science for Life Laboratory, SciLifeLab,SeRC - Swedish e-Science Research Centre,Biofysik

Lindahl, Erik, 1972- (author): KTH,Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),KTH Royal Institute of Technology, Sweden,SeRC - Swedish e-Science Research Centre,Science for Life Laboratory, SciLifeLab,Biofysik,Stockholm Univ, Dept Biophys & Biochem, Sci Life Lab, Solna, Sweden.

ERCO Pharma AB, Sci Life Lab, Solna, Sweden Tillämpad fysik (creator_code:org_t)

Biophysical Society, 2022
2022
English.
In: Biophysical Journal. - : Biophysical Society. - 0006-3495 .- 1542-0086. ; 121:20, s. 3837-3849

Related links:: https://doi.org/10.1...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; https://urn.kb.se/re...; http://kipublication...; show less...

Abstract Subject headings

A molecular-level understanding of skin permeation may rationalize and streamline product development, and improve quality and control, of transdermal and topical drug delivery systems. It may also facilitate toxicity and safety assessment of cosmetics and skin care products. Here, we present new molecular dynamics simulation approaches that make it possible to efficiently sample the free energy and local diffusion coefficient across the skin’s barrier structure to predict skin permeability and the effects of chemical penetration enhancers. In particular, we introduce a new approach to use two-dimensional reaction coordinates in the accelerated weight histogram method, where we combine sampling along spatial coordinates with an alchemical perturbation virtual coordinate. We present predicted properties for 20 permeants, and demonstrate how our approach improves correlation with ex vivo/in vitro skin permeation data. For the compounds included in this study, the obtained log KPexp-calc mean square difference was 0.9 cm2 h−2.

By the author/editor: Lundborg, Magnus; Wennberg, Christ ...; Lidmar, Jack, 19 ...; Hess, Berk; Lindahl, Erik, 1 ...; Norlén, Lars

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biophysics

By the university: Stockholm University; Royal Institute of Technology; Karolinska Institutet

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