3 research outputs found
Molecular Dynamics and Metadynamics Insights of 1,4-Dioxane-Induced Structural Changes of Biomembrane Models
1,4-dioxane is a cytotoxic B2 type human carcinogen, a serious water pollutant produced
solely by industrial activity. The effect of 1,4-dioxane on phospholipid membrane models composed
by DPPC and its branched isomer (IPPC) was investigated using MD simulations. Clear and polluted
membranes were compared by membrane parameters such as APL, VPL, compressibility modulus,
membrane thickness and orderliness of lipid tails. While neat systems significantly differ from each
other, the presence of the pollutant has the same effect on both types of lipid membranes: high density
of dioxane appears at the vicinity of ester groups which pushes away lipid headgroups from each
other, leading to an overall change in lipid structure: APL and VPL grows, while the orderliness of
lipid tails, membrane thickness and compressibility modulus decreases. Orientational preferences of
water and dioxane molecules were also investigated and different membrane regions have been
specified according to the stance of water molecules. Free energy profile for 1,4-dioxane penetration
mechanism into DPPC membranes was carried out using metadynamics for two different
concentrations of the pollutant (c1=7.51 g/dm3
, c2=75.10 g/dm3
), which showed that the higher the
concentration is, the lower the free energy of penetration gets. Only a small free energy barrier was
found in the headgroup region and accumulation of dioxane is thermodynamically unfavored in the
middle of the bilayer. The penetration mechanism has been described in detail based on the
orientational preference of 1,4-dioxane molecules and the free energy profiles