Molecular dynamics simulations of glyphosate in a DPPC lipid bilayer

Extensive molecular dynamics simulations have been performed to study the effect of glyphosate (in their neutral and charged forms, GLYP and GLYP^2-, respectively) on fully hydrated DiPalmitoylPhosphatidylCholine (DPPC) lipid bilayer. First, we calculated the free energy profile (using the Umbrella Sampling technique) for both states of charge of glyphosate. The minimum value for the free energy for GLYP is ∼-60 kJ mol^-1 located at z = ±1.7 nm (from the lipid bilayer center), and there is almost no maximum at the center of the lipid bilayer. By contrast, the minimum for GLYP^2- is ∼-35 kJ mol^-1 located at z = ± 1.4 nm (from the lipid bilayer center), and the maximum reaches ∼35 kJ mol^-1 at the center of the lipid bilayer. Then, different lipid bilayer properties were analyzed for different glyphosate:lipid (G:L) ratios. The mean area per lipid was slightly affected, increasing only 5% (in the presence of glyphosate at high concentrations), which is in agreement with the slight decrease in deuterium order parameters. As for the thickness of the bilayer, it is observed that the state of charge produces opposite effects. On one hand, the neutral state produces an increase in the thickness of the lipid bilayer; on the other, the charged form produces a decrease in the thickness, which not depend linearly on the G:L ratios, either. The orientation of the DPPC head groups is practically unaffected throughout the range of the G:L ratios studied. Finally, the mobility of the lipids of the bilayer is strongly affected by the presence of glyphosate, considerably increasing its lateral diffusion coefficient noteworthy (one order of magnitude), with increasing G:L ratio.