Interaction of neurotransmitters with a phospholipid bilayer: A molecular dynamics study

•Neurotransmitter interactions with DPPC varied reflecting the nature of the solutes.•Low absorption/affinity for charged neurotransmitters towards zwitterionic bilayer.•Zwitterionic and polar molecules penetrating and located at lipid glycerol backbone.•The general picture that emerges is that electrostatic interactions are predominant.•Significant amounts of water co-partitioned with the solutes into the membrane. We have performed a series of molecular dynamics simulations to study the interactions between the neurotransmitters (NTs) γ-aminobutyrate (GABA), glycine (GLY), acetylcholine (ACH) and glutamate (GLU) as well as the amidated/acetylated γ-aminobutyrate (GABAneu) and the osmolyte molecule glycerol (GOL) with a dipalmitoylphosphatidylcholine (DPPC) bilayer. In agreement with previously published experimental data, we found the lowest membrane affinity for the charged molecules and a moderate affinity for zwitterionic and polar molecules. The affinity can be ranked as follows: ACH–GLU