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

Abstract

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.

Ultrafast phosphate hydration dynamics in bulk H2O

“…Molecular dynamics simulations found that water molecules connect different phospholipids and that the lifetime of these water bridges is up to 50 ps. 47 Thus, the water shell around phosphate groups in phospholipids is comparably rigid and fluctuating molecular motions to a substantial extent suppressed. Moreover, due to the tilt of phospholipid head groups, this hydration shell water is partly shielded from the surrounding bulk, i.e., the electric force exerted by bulk water fluctuations on both interfacial water and PO − 2 oscillators is much weaker than the dipole forces originating from the head groups.…”

Free energy landscapes of sodium ions bound to DMPC–cholesterol membrane surfaces at infinite dilution

“…CHARMM-GUI 21,22 was employed to generate six sets of lipid bilayers with cholesterol concentrations [CHOL] varying between 0% and 50%. Each system consisted of 72 cholesterol / dimyristoylphosphatidylcholine (DMPC) 23,24 molecules, 3600 water molecules described by the modified TIP3P model 25,26 , and a pair of Na + and Cl − described by the CHARMM36 force field 27,28 . In contrast to other force fields (such as GROMOS), the CHARMM36 force field generates a less pronounced adsorption of Na + ions on phosphatidylcholine (PC) membranes, which was shown to be consistent with structural Xray measurements and experiments on chain ordering of PC lipid bilayers in the presence of NaCl 29 .…”

Effects of phospholipid unsaturation on the bilayer nonpolar region

“…Details concerning the construction of the POPC and PEPC molecules and subsequently bilayers, as well as the initial simulations of these bilayers, were described in Murzyn et al (36). Details concerning the DMPC bilayer were described in Pasenkiewicz-Gierula et al (44,45).…”