Open AccessEffects of Cholesterol on the Partitioning of a Drug Molecule in Lipid Bilayers
Author(s) -
Yuqin Yang,
Hao Dong,
HuanXiang Zhou
Publication year - 2021
Publication title -
the journal of physical chemistry. b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 392
eISSN - 1520-6106
pISSN - 1520-5207
DOI - 10.1021/acs.jpcb.1c02436
Subject(s) - membrane , chemistry , lipid bilayer , bilayer , cholesterol , permeation , molecule , molecular dynamics , biophysics , partition coefficient , biochemistry , chromatography , computational chemistry , organic chemistry , biology
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 perturbation of the bilayer structure and dynamics. Surrounding lipids stabilize amantadine by having their tails wrapped around the drug molecule, and this ability is compromised when cholesterol is present to increase the order in lipid tails. The atomic details on interactions with lipids and perturbations by cholesterol revealed here provide insight into membrane partition and delivery of drug molecules to their targets.