The Distributions and Orientations of Retinoids in Retinal Membranes Studied with All-Atom Molecular Dynamics Simulations

Abstract

Understanding the transport of retinoids in lipid bilayers is essential to describe the binding to photoreceptors or retinoid-binding proteins involved in the visual cycle. Utilizing all-atom molecular simulations, we demonstrate how 11-cis retinal, all-trans retinal and all-trans retinol distribute and orient in lipid bilayers with different levels of unsaturation, head group and the presence of cholesterol, characteristic of retinal membranes. We have found that all-trans retinol is more depleted in the membrane core (with a substantially lower density relative to retinal) and less flexible in its orientation (with a more parallel alignment to the membrane normal) than its retinal counterpart. We shall discuss how these results pertain to the vision cycle. In particular, the restricted distribution of retinol may assist the removal of all-trans retinol from the rod outer segment(ROS) membranes by facilitating its binding to certain retinoid-binding proteins. On the other hand, the higher accessibility of the membrane core to all-trans retinal and its flexible orientation may assist its release from bleached photoreceptors. Furthermore, we demonstrate that the presence of cholesterol increases the concentration of 11-cis retinal in the membrane core and will explain how this is consistent with the roles of plasma and disk membranes in the retinoid cycle.