Abstract
Lutein, a hydroxylated carotenoid, is a pigment synthesised by plants and bacteria. Animals are unable to synthesise lutein, nevertheless, it is present in animal tissues, where its only source is dietary intake. Both in plants and animals, carotenoids are associated mainly with membranes where they carry out important physiological functions. Their trafficking to and insertion into membranes are not well recognised due to experimental difficulties. In this paper, a computational approach is used to elucidate details of the dynamics and energetics of lutein intercalation from the water to the phospholipid bilayer phase. The dynamics is studied using molecular dynamics simulation, and the energetics using umbrella sampling. Lutein spontaneous insertion into the bilayer and translocation across it proceed via formation of hydrogen bonds between its hydroxyl groups and water and/or phospholipid oxygen atoms as well as desolvation of its polyene chain. As lutein molecule is asymmetric, its bilayer intercalation is also asymmetric. The course of events and timescale of the intercalation are different from those of helical peptides. The time of full lutein intercalation ranges from 20 to 100 ns and its final orientation is predominately vertical. Nevertheless, some lutein molecules are in the final horizontal position and some aggregate in the water phase and remain there for the whole simulation time. The highest energy barrier for the intercalation process is ~2.2 kcal/mol and the energy gain is ~18 kcal/mol. The results obtained for lutein can be applied to other xanthophylls and molecules of a similar structure.