The impact of five different imidazolium-based ionic liquids (ILs) diluted in water on the properties of a bacterial plasma membrane is investigated using molecular dynamics (MD) simulations. Cations considered are 1-octyl-3-methylimidazolium (OMIM), 1-octyloxymethyl-3-methylimidazolium (OXMIM), and 1-tetradecyl-3-methylimidazolium (TDMIM), as well as the anions chloride and lactate. The atomistic model of the membrane bilayer is designed to reproduce the lipid composition of the plasma membrane of Gram-negative Escherichia coli. Spontaneous insertion of cations into the membrane is observed in all ILs. Substantially more insertions of OMIM than of OXMIM occur and the presence of chloride reduces cation insertions compared to lactate. In contrast, anions do not adsorb onto the membrane surface nor diffuse into the bilayer. Once inserted, cations are oriented in parallel to membrane lipids with cation alkyl tails embedded into the hydrophobic membrane core, while the imidazolium-ring remains mostly exposed to the solvent. Such inserted cations are strongly associated with one to two phospholipids in the membrane. The overall order of lipids decreased after OMIM and OXMIM insertions, while on the contrary the order of lipids in the vicinity of TDMIM increased. The short alkyl tails of OMIM and OXMIM generate voids in the bilayer that are filled by curling lipids. This cation induced lipid disorder also reduces the average membrane thickness. This effect is not observed after TDMIM insertions due to the similar length of cation alkyl chain and the fatty acids of the lipids. This lipid-mimicking behavior of inserted TDMIM indicates a high membrane affinity of this cation that could lead to an enhanced accumulation of cations in the membrane over time. Overall, the simulations reveal how cations are inserted into the bacterial membrane and how such insertions change its properties. Moreover, the different roles of cations and anions are highlighted and the fundamental importance of cation alkyl chain length and its functionalization is demonstrated.

This paper reports an all-atom molecular dynamics simulation of lipid bilayers with different cholesterol/sphingomyelin molar ratios. Our results reveal structural and dynamic changes suggesting the random distribution of lipids along the bilayer planes is supplanted at cholesterol concentrations above 30 mol % by the formation of a liquid-ordered phase, which is thought to be the precursor to lipid raft formation. The packing of molecules in the bilayer is shown to be associated with the hydrogen bonding between cholesterol and sphingomyelin. The molecules tend to migrate toward distributions in which the sphingomyelin molecule forms on average one hydrogen bond with a cholesterol molecule. The threshold for activation of this packing trend coincides with the experimentally determined threshold membrane activity of a cytolytic protein ostreolysin, which binds to and permeabilizes cholesterol-sphingomyelin bilayers containing more than 30 mol % cholesterol.

Hydration of histamine was examined by infrared spectroscopy and Car-Parrinello molecular dynamics simulation. Histamine is a neurotransmitter and inflammation mediator, which at physiological pH conditions is present mainly in monocationic form. Our focus was on the part of vibrational spectra that corresponds to histamine N-H stretching, since these degrees of freedom are essential for its interactions with either water molecules or transporters and receptors. Assignment of the experimental spectra revealed a broad feature between 3350 and 2300 cm(-1), being centered at 2950 cm(-1), which includes a mixed contribution from the ring N-H and the aminoethyl N-H stretching vibrations. Computational analysis was performed in two ways: first, by making Fourier transformation on the autocorrelation function of all four N-H bond distances recorded during CPMD run, and second, and most importantly, by incorporating quantum effects through applying an a posteriori quantization of all N-H stretching motions utilizing our snapshot analysis of the fluctuating proton potential. The one-dimensional vibrational Schrödinger equation was solved numerically for each snapshot, and the N-H stretching envelopes were calculated as a superposition of the 0→1 transitions. The agreement with the experiment was much better in the case of the second approach. Our calculations clearly demonstrated that the ring amino group absorbs at higher frequencies than the remaining three amino N-H protons of the protonated aminoethyl group, implying that the chemical bonding in the former group is stronger than in the three amino N-H bonds, thus forming weaker hydrogen bonding with the surrounding solvent molecules. In this way the results of the simulation complemented the experimental spectrum that cannot distinguish between the two sets of protons. The effects of deuteration were also considered. The resulting N-D absorption is narrower and red-shifted. The presented methodology is of general applicability to strongly correlated systems, and it is particularly tuned to provide computational support to vibrational spectroscopy. Perspectives are given for its future applications in computational studies of tunneling in enzyme reactive centers and for receptor activation.