Simulating POPC and POPC/POPG Bilayers: Conserved Packing and Altered Surface Reactivity.

Molecular dynamics (MD) simulation is a popular technique to study bilayer structural properties, but it has not been widely used in mixed bilayers of neutral and charged lipids. Here, we present results from constant temperature and pressure MD simulations of a 2-oleoyl-1-pamlitoyl-sn-glyecro-3-phosphocholine (POPC) bilayer containing 23% 2-oleoyl-1-pamlitoyl-sn-glyecro-3-glycerol (POPG). The simulations were performed using the recently updated CHARMM force field and involved two bilayers of 104 and 416 lipids. A control simulation of a pure POPC bilayer of 128 lipids yielded equilibrium structural properties that compare very well with experimental data. The average equilibrium properties of the mixed bilayer systems were very similar to those of the pure POPC. However, nearly one-half of all the POPG lipids were found to be involved in hydrogen bonding with POPC lipids. Furthermore, the hydration of the mixed bilayer is different from that of the pure POPC, with the former inducing ordering of water molecules at longer distances. Thus, a phospholipid bilayer with ∼23% negative charge content in the liquid crystalline phase differs from its neutral counterpart only at the headgroup.