Atomistic molecular dynamics simulations of the interactions of oleic and 2-hydroxyoleic acids with...

Fatty oleic acid (OA) and, recently, its derivative 2-hydroxyoleic acid (2OHOA) have been reported to display an important therapeutic activity. To understand better these therapeutic effects at the molecular and cellular levels, in this work we have carried out molecular dynamics simulations to elucidate the structural and dynamical changes taking place in model 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers upon insertion of rising concentrations of these two fatty acids. The simulations are performed using a united-atoms model to describe both the phospholipids and the fatty acids. The process of insertion of the fatty acids from the aqueous phase into the bilayers is simulated first, showing that it is feasible and may lead to some degree of phase separation within the bilayer. The interactions of the embedded homogeneously dispersed fatty acids with the phospholipid chains of the bilayers are then simulated at different concentrations of the fatty acids. The results from these simulations show that accumulation of OA and 2OHOA up to high concentrations induces only small structural changes in the bilayers. An increase of the mobility of the lipid and fatty acid chains at rising fatty acid concentrations is also observed, which is more marked for the fatty acid chains, along with an enhancement of the permeability of the bilayers to the hydrophobic penetrant.