Effects of Cholesterol on the Partitioning of a Drug Molecule in Lipid Bilayers.

ABSTRACT: Drug molecules either bind to membrane-bound targets or permeate through cell membranes to reach intracellular targets, and hence, their membrane partition and permeation are of great importance. Here, we studied the effects of cholesterol on the partition of amantadine, an antiflu drug molecule, into 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayers using molecular dynamics simulations. The membrane partition of amantadine is sensitive to the cholesterol mole fraction (x_chol). In the absence of cholesterol, amantadine is stably bound in membranes, but at x_chol = 32%, it can escape to the aqueous phase, in agreement with recent experiments. The reduced membrane partition of amantadine at a high cholesterol content is mainly due to the perturbat

SUBMITTER: Yang Y 

PROVIDER: S-EPMC8159892 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature