Small molecule interaction with lipid bilayers: A molecular dynamics study of chlorhexidine

[Display omitted] •MD simulations were used to examine the drug chlorhexidine in DMPC membranes.•The effect of molecular charge and concentration was studied.•Simulation results were in agreement with NMR and neutron scattering experiments.•The effect of chlorhexidine was highly dependent on the molecule's charge.•The effect was a thinning of the membrane, and increase in the area per lipid. Chlorhexidine (CHX) is an effective anti-bacterial agent whose mode of action is thought to be the disruption of the cell membrane. We tested the capability of the Slipids all atom force fields using data from neutron scattering and NMR experiments on the drug chlorhexidine in a 1,2-dimyrisoyl-3-sn-phosphatidylcholine (DMPC) membrane. Since it is not known what the charge of the CHX molecule is inside an apolar environment, a neutral, as well as a +1 and +2 charge model for the molecule were created and tested at several concentrations. This study shows that the location of CHX is minorly dependent on concentration, and dominantly reliant on the charge. The effect of adding CHX to DMPC is a thinning of the membrane, thus increasing the area per lipid.