Menthol Binding to the Human α4β2 Nicotinic Acetylcholine Receptor Facilitated by Its Strong Partitioning in the Membrane.

ABSTRACT: We utilize various computational methodologies to study menthol's interaction with multiple organic phases, a lipid bilayer, and the human α4β2 nicotinic acetylcholine receptor (nAChR), the most abundant nAChR in the brain. First, force field parameters developed for menthol are validated in alchemical free energy perturbation simulations to calculate solvation free energies of menthol in water, dodecane, and octanol and compare the results against experimental data. Next, umbrella sampling is used to construct the free energy profile of menthol permeation across a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer. The results from a flooding simulation designed to study the water-membrane partitioning of menthol in a POPC lipid bilayer are used to determine the penetr

SUBMITTER: Shahoei R 

PROVIDER: S-EPMC7094167 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature