Properties of hydrated excess protons near phospholipid bilayers

The behavior of the hydrated excess proton near different lipid membranes is studied with the third generation of the multistate empirical valence bond (MS-EVB3) model [Wu, Y. J.; Chen, H. N.; Wang, F.; Paesani, F.; Voth, G. A. J. Phys. Chem. B 2008, 112, 467]. Dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE), and dioleoylphosphatidylglycerol (DOPG) are selected as example lipids. In spite of the differences of the head groups, the molecular dynamics simulations show that all the lipid membranes have a proton-collecting antenna effect with no free energy barrier between the bulk water and interface regions. By comparison with classical hydronium model simulations, it is found that an appropriate description of proton Grotthuss shuttling and associated charge defect delocalization are necessary to obtain the correct free energy profile for the hydrated excess proton. In addition, nanosecond time scale sampling is essential to evaluate the free energy profiles, because certain slow motions are needed to stabilize the excess proton in the deep membrane interface region. It is also found that the lateral diffusion coefficients are 1 order of magnitude smaller in the interface region than in bulk water for all the lipids. These coefficients are almost the same as those of the lipid head groups. Finally, since the lipid phosphates may possibly be protonated due to the proton antenna effect of the membrane, phosphate group protonation is investigated and discussed within the MS-EVB framework.