HYDROGEN-BONDING OF WATER TO PHOSPHATIDYLCHOLINE IN THE MEMBRANE AS STUDIED BY A MOLECULAR-DYNAMICS SIMULATION - LOCATION, GEOMETRY, AND LIPID-LIPID BRIDGING VIA HYDROGEN-BONDED WATER

Hydrogen (H-) bonding between water and phosphatidylcholine was studie d using a molecular dynamics simulation of a hydrated phosphatidylchol ine bilayer membrane in the liquid crystalline phase. A membrane in th e liquid-crystalline phase composed of 72 L-alpha-dimyristoylphosphati dylcholine (DMPC) and 1622 water molecules was generated, starting fro m 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, Th e thermodynamic and structural parameters became stable after the equi libration period of 1100 ps, and the trajectory of the system obtained during the following 500 ps agreed well with most of the published ex perimental data. Each DMPC molecule forms 5.3 I-I-bonds with water, wh ile 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 oxy gens (4.0 H-bonds) and the carbonyl oxygens (similar to 1.0 H-bonds). Of DMPC's H-bonds, 1.7 are formed with water molecules that are simult aneously H-bonded to two different DMPC oxygens (bridging water). In e ffect, approximately 70% of the DMPC molecules are linked by water mol ecules 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 ar e linked by more than one parallel bridge. These results suggest a pos sibility that water bridges are involved in reducing head group mobili ty and in stabilizing the membrane structure. Non-ester phosphate oxyg en of DMPC makes one, two, or three H-bonds with water, but two H-bond s are formed most often (approximate to 60%). In the case where two H- bonds are formed on non-ester phosphate or carbonyl oxygens, the avera ge geometry of H-bonding is planar trigonal (in the case of water oxyg en with two H-bonds, geometry is steric tetragonal). When oxygen atoms form three H-bonds, the geometry of H-bonding is steric tetragonal bo th 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.