Solvated phospholipid bilayer

The first simulations of fully solvated phospholipid bilayers appeared in the early 90 s. °" These works showed that atomistic MD simulations of membranes were feasible (up to hundreds of picoseconds) and represented a powerful tool to study microscopic properties of... 

This chapter has given an overview of the structure and dynamics of lipid and water molecules in membrane systems, viewed with atomic resolution by molecular dynamics simulations of fully hydrated phospholipid bilayers. The calculations have permitted a detailed picture of the solvation of the lipid polar groups to be developed, and this picture has been used to elucidate the molecular origins of the dipole potential. The solvation structure has been discussed in terms of a somewhat arbitrary, but useful, definition of bound and bulk water molecules. 

Most drug-like molecules dissolved in water form hydrogen bonds with the solvent. When such a molecule transfers from water into a phospholipid bilayer, the solute-water hydrogen bonds are broken (desolvation), as new solute-lipid H bonds form in the lipid phase. The free-energy difference between the two states of solvation has direct impact on the ability of the molecules to cross biological barriers. 

Fig. 3.18 (A) Schematic drawing of a phospholipid bilayer containing a membrane-solvated globular protein that has a sodium channel in the closed configuration. (B) The globular protein has expanded in conformation to allow a sodium ion influx. (C) Anesthetic molecules have fluidized the entire bilayer and destroyed the regions of solid phase.

Phospholipids are amphipathic molecules, that is, they have parts of different polarity. The fatty acyl chains are nonpolar and hydrophobic whereas the phosphoryl alcohol head group is polar and can be solvated by H20. Phospholipids form bimolecular membranes in which the hydrophobic fatty acyl chains are located in the interior of the membrane (away from H20) and the head groups are on the surface (on either side of the membrane) and exposed to H20. Representing phospholipids as =0 (where = represents the fatty acyl chain and O the head group), we can represent such a phospholipid bilayer thus ... 

The non-polar component of the solvation free energy is especially important for implicit membrane models as it decreases from a significant positive contribution in aqueous solvent to near zero at the center of the phospholipid bilayer. Without a non-polar term, even hydrophobic solutes would in fact prefer the high-dielectric environment where the electrostatic solvation free energy is more favorable than in a low-dielectric medium. The functional form of the non-polar term may follow a simple switching function [79,80], a calculated free energy insertion profile for molecular oxygen [82,84], or may be parameterized as well with respect to simulation or experimental data. 

Recently, a molecular dynamics study of the phospholipid DLPE was reported by Damodaran et al. using a united atom model. The model was built from the crystal structure of DLPE reported by Elder et al. The fully hydrated DLPE bilayer has an interlamellar water layer of 5 A. The bilayer was solvated by 553 SPCE waters ( 11 water molecules/lipid) in the head group region. This lipid has a gel-to-liquid-crystalline transition temperature of... 

Biological membranes are lipid bilayers in which the hydrophobic hydrocarbon tails are packed in the center of the bilayer and the ionic head groups are exposed on the surface to interact with water (Figure 18.11). The hydrocarbon tails of membrane phospholipids provide a thin shell of nonpolar material that prevents mixing of molecules on either side. The nonpolar tails of membrane phospholipids thus provide a barrier between the interior of the cell and its surroundings. The polar heads of lipids are exposed to water, and they are highly solvated. Little exchange, known colloquially as "flip-flop," occurs between lipids on the outer and... 

The most important bilayers are formed by the phospholipids, shown in Figure 12.1(a).They form the membrane that covers the surface of our blood cells. Bilayer structures are stabilized by solvation of the head groups by water and by the nearly total avoidance of water by the hydrophobic hydrocarbon tails. We observe the same pattern in many self-assemblies found in nature, such as micelles, reverse micelles, and microemulsions, discussed later. 

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