Interaction of transported drugs with the lipid bilayer and P-glycoprotein through a solvation exchange mechanism.

ABSTRACT: Broad substrate specificity of human P-glycoprotein (ABCB1) is an essential feature of multidrug resistance. Transport substrates of P-glycoprotein are mostly hydrophobic and many of them have net positive charge. These compounds partition into the membrane. Utilizing the energy of ATP hydrolysis, P-glycoprotein is thought to take up substrates from the cytoplasmic leaflet of the plasma membrane and to transport them to the outside of the cell. We examined this model by molecular dynamics simulation of the lipid bilayer, in the presence of transport substrates together with an atomic resolution structural model of P-glycoprotein. Taken together with previous electron paramagnetic resonance studies, the results suggest that most transported drugs are concentrated near the surface zone of th

SUBMITTER: Omote H 

PROVIDER: S-EPMC1459527 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature