Conformational Analysis of Hexagonal Arrangements of Phosphatidylcholine Head Groups with Bound Waters by Molecular Mechanics

Yoshiro NAKATA*, Akira TAKAHASHI*1 and Toshiharu TAKIZAWA*1



In phospholipids-water systems, head groups of lipid molecules have been known to reorientate in the surface of the bilayer plane with the correlation time of the order of 1 ns[1]. It is also known that several water molecules are bound to the phosphate group in the head group with a lifetime much greater than the reorientation correlation time of the head group[2]. These facts have suggested that hydrated water molecules may be kept tightly bound to the head group while it is rotating. Recently we have obtained direct evidence for this by the study of the spin-lattice relaxation for the proton of water(HDO) bound to the head group in dipalmitoylphosphatidyl- choline(DPPC)-D2O system[3].
In this paper, we report the favorable sites for hydration of the phosphate group in the phosphatidylcholine head group calculated by molecular mechanics.


The MMHS-ex (Molecular Model Handling System expanded edition) software system[4,5] was used to carry out the model building and the molecular mechanics calculations.
Configuration of phosphatidylcholine head group;The bond distances and bond angles were taken from the crystal X-ray structures of glyceryl- phophorylethanolamine(GPE) and glycerylphosphorylcholine(GPC)[6,7]. The torsional angles used are a1=180, a2=60, a3=65, a4=180, and a5=300 according to the conformation of the crystallographic date of GPC. The trans conformation about a4 occurs for strong hydration of the phosphate group[8,9]. The head group is assumed to be rotating around the glycerol C2-C3 axis, which is almost perpendicular to the bilayer plane.

Figure 1. Chemical Structure of phosphatidylcholine head group and torsional rotation angle definitions.

Hexagonal arrangement of phosphatidylcholine head groups in a bilayer plane; It is assumed that the lipid molecules are packed in a hexagonal lattice, and that each lipid head group reorients randomly about the bilayer normal. The distance between neighboring molecules is 8.7A, which gives the surface area of 76A2 per molecule at a temperature near the main transition in the La phase for DPPC[10].
Two head molecules were placed in distance 8.7A as the same orientation in same plane. Then the intermolecular energy scan was performed by simultaneously varying C2-C3 bonds from 0 to 360 at 5 intervals. The minimum energy orientation was selected in Fig. 2 as the state I. The state II and III were obtained by rotating two molecules to 60 and 120 simultaneously around the C2-C3 bonds.

Figure 2. The calculated potential   Figure 3. Hexagonal arrangement 
function around C2-C3 bonds          model of phosphatidylcholine 
in two head group system.            head groups.

Results and Discussion

Conformation Study of the favorable sites for hydration of the phosphate group in the head group at the hexagonal arrangement; One water molecule is placed in the position where the distance between H- atom in water and O-atom in phosphate group is 1.45A and the angle between P=O bond and O---H directions is 110. Then the conformation scan was performed by varying P=O bond from 0 to 360 at 5 intervals. Five favorable sites, resulting in minimum or lower energy, were selected, and separated from each other in rotational angle by 120. The calculated rotational functions are shown in Figure 4a and 4b.
The result shows that there are three favorable hexagonal arrangements of the head groups, in which five water molecules can be placed around each phosphate group. The most favorable arrangement of head groups viewed perpendicular to the layer surface is given in Figure 5. The water molecules are drawn only about the central head group. The others are obtained by rotating all the head groups simultaneously about each rotation axis towards the same direction by the angle of 120 or -120.

Figure 4a. The calculated potential   Figure 4b. The calculated potential
function around P=O3 bond.            function around P=O4 bond.

Figure 5. A hexagonal arrangement of the phosphatidylcholine head groups model.

We have studied experimentally the spin-lattice relaxation for the proton of water(HDO) bound to the head group in dipalmitoylphosphatidylcholine (DPPC)-D2O system. Based on the preferred conformations and orientations of the head groups, the relaxation rate of bound water can be calculated, which seems fairly agreeable to the experimental value[11].


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