Hydrogen (H-) bonding between water and phosphatidylcholine was studied using a molecular dynamics simulation of a hydrated phosphatidylcholine bilayer membrane in the liquid crystalline phase. A membrane in the liquid-crystalline phase composed of 72 l-α-dimyristoylphosphatidylcholine (DMPC) and 1622 water molecules was generated, starting from the crystal structure of DMPC. At the beginning of the equilibration process, the temperature of the system was raised to 550 K for 20 ps, which was effective in breaking the initial crystalline structure. The thermodynamic and structural parameters became stable after the equilibration period of 1100 ps, and the trajectory of the system obtained during the following 500 ps agreed well with most of the published experimental data. Each DMPC molecule forms 5.3 H-bonds with water, while only 4.5 water molecules are H-bonded to DMPC. The primary targets of water for the formation of H-bonds are the non-ester phosphate oxygens (4.0 H-bonds) and the carbonyl oxygens (∼1.0 H-bonds). Of DMPC's H-bonds, 1.7 are formed with water molecules that are simultaneously H-bonded to two different DMPC oxygens (bridging water). In effect, approximately 70% of the DMPC molecules are linked by water molecules and form clusters of two to seven DMPC molecules. Approximately 70% of the intermolecular water bridges are formed between non-ester phosphate oxygens. The rest are formed between non-ester phosphate and carbonyl oxygens. About half of the intermolecular water bridges are involved in formation of multiple bridges, where two DMPC molecules are linked by more than one parallel bridge. These results suggest a possibility that water bridges are involved in reducing head group mobility and in stabilizing the membrane structure. Non-ester phosphate oxygen of DMPC makes one, two, or three H-bonds with water, but two H-bonds are formed most often (≈60%). In the case where two H-bonds are formed on non-ester phosphate or carbonyl oxygens, the average geometry of H-bonding is planar trigonal (in the case of water oxygen with two H-bonds, geometry is steric tetragonal). When oxygen atoms form three H-bonds, the geometry of H-bonding is steric tetragonal both for non-ester phosphate and water oxygens. On average, H-bonds make nearly right angles with each other when two or three water molecules are bound to the same DMPC oxygen, but the distribution of the angle is broad.

Molecular dynamics simulation of the hydrated dimyristoylphosphatidylcholine (DMPC) bilayer membrane in the liquid-crystalline phase was carried out for 5 ns to study the interaction among DMPC headgroups in the membrane/water interface region. The phosphatidylcholine headgroup contains a positively charged choline group and negatively charged phosphate and carbonyl groups, although it is a neutral molecule as a whole. Our previous study (Pasenkiewicz-Gierula, M., Y. Takaoka, H. Miyagawa, K. Kitamura, and A. Kusumi. 1997. J. Phys. Chem. 101:3677-3691) showed the formation of water cross-bridges between negatively charged groups in which a water molecule is simultaneously hydrogen bonded to two DMPC molecules. Water bridges link 76% of DMPC molecules in the membrane. In the present study we show that relatively stable charge associations (charge pairs) are formed between the positively and negatively charged groups of two DMPC molecules. Charge pairs link 93% of DMPC molecules in the membrane. Water bridges and charge pairs together form an extended network of interactions among DMPC headgroups linking 98% of all membrane phospholipids. The average lifetimes of DMPC-DMPC associations via charge pairs, water bridges and both, are at least 730, 1400, and over 1500 ps, respectively. However, these associations are dynamic states and they break and re-form several times during their lifetime.

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