Molecular orbital studies on the conformation of phospholipids. II. Preferred conformations of hydrocarbon chains and molecular organization in biomembranes

Abstract

The preferred conformations of the nonpolar β and γ (hydrocarbon) chains in phospholipids have been derived using EHT and CNDO calculations. These calculations indicate that the possible conformations of phospholipids are highly restricted. The calculations find support from X-ray diffraction studies and NMR measurements on model compounds. When considering conformations relevant to structures in cell membranes, a further selection is possible because of the fact that in aqueous solutions hydrophobic interactions stabilize an arrangement where the hydrocarbon chains (β and γ ) are stacked almost parallel to one another, leading to a bilayer structure. The various models for β and γ -chains which satisfy this condition have been compared and it has been shown that of these only four are favoured by energy considerations. These arrangements differ from one another in the orientation of the β-chain and γ-chains in the interior of the bilayer structure. A low energy pathway connects these conformations and thus the molecule can easily flip from one stable bilayer arrangement to another. The possible conformations of the polar group (α ) are likewise restricted. The proposed model provides explanations to a number of dynamic and static properties of phospholipids, in particular to the observed NMR coupling constants, ¹H and ¹³C relaxation times, studies based on ESR spin labels and the observed X-ray diffraction results on model compounds.