Partitioning of Benzoic Acid into 1,2-Dimyristoyl-sn-glycero-3-phosphocholine and Blood-Brain Barrier Mimetic Bilayers.

Journal of Chemical Information and Modeling
Christopher M SiwyDmitri K Klimov

Abstract

Using an all-atom explicit water model and replica exchange umbrella sampling simulations, we investigated the molecular mechanisms of benzoic acid partitioning into two model lipid bilayers. The first was formed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipids, whereas the second was composed of an equimolar mixture of DMPC, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, palmitoylsphingomyelin, and cholesterol to constitute a blood-brain barrier (BBB) mimetic bilayer. Comparative analysis of benzoic acid partitioning into the two bilayers has revealed qualitative similarities. Partitioning into the DMPC and BBB bilayers is thermodynamically favorable although insertion into the former lowers the free energy of benzoic acid by approximately an additional 1 kcal mol-1. The partitioning energetics for the two bilayers is also largely similar based on the balance of benzoic acid interactions with apolar fatty acid tails, polar lipid headgroups, and water. In both bilayers, benzoic acid retains a considerable number of residual water molecules until reaching the bilayer midplane where it experiences nearly complete dehydration. Upon insertion into the bilayers, benzoic acid undergoes several rotations primarily deter...Continue Reading

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Mar 4, 2021·The Journal of Physical Chemistry. B·Christopher M SiwyDmitri K Klimov

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