Partition, orientation and mobility of ubiquinones in a lipid bilayer

Ubiquinone is the universal mobile charge carrier involved in biological electron transfer processes. Its redox properties and biological function depend on the molecular partition and lateral diffusion over biological membranes. However, ubiquinone localization and dynamics within lipid bilayers are long debated and still uncertain. Here we present molecular dynamics simulations of several ubiquinone homologs with variable isoprenoid tail lengths complexed to phosphatidylcholine bilayers. Initially, a new force-field parametrization for ubiquinone is derived from and compared to high level quantum chemical data. Free energy profiles for ubiquinone insertion in the lipid bilayer are obtained with the new force-field. The profiles allow for the determination of the equilibrium location of ubiquinone in the membrane as well as for the validation of the simulation model by direct comparison with experimental partition coefficients. A detailed analysis of structural properties and interactions shows that the ubiquinone polar head group is localized at the water-bilayer interface at the same depth of the lipid glycerol groups and oriented normal to the membrane plane. Both the localization and orientation of ubiquinone head groups do not change significantly when increasing the number of isoprenoid units. The isoprenoid tail is extended and packed with the lipid acyl chains. For ubiquinones with long tails, the terminal isoprenoid units have high flexibility. Calculated ubiquinone diffusion coefficients are similar to that found for the phosphatidylcholine lipid. These results may have further implications for the mechanisms of ubiquinone transport and binding to respiratory and photosynthetic protein complexes.