Concentration effect of cimetidine with POPC bilayer: a molecular dynamics simulation study. Issue 15 (12th October 2016)

• Record Type: Journal Article
• Authors: Wang, Huanjie; Meng, Fancui
• Is Part Of: Molecular simulation. Volume 42:Issue 15(2016)
• Page Start: 1292
• Page End: 1297
• Publication Date: 2016-10-12
• Subjects: Molecular dynamics -- cimetidine -- potential of mean force (PMF) -- POPC; Molecular dynamics -- Computer simulation -- Periodicals; Statistical mechanics -- Computer simulation -- Periodicals; 539.6
• DOI: 10.1080/08927022.2016.1185793
• Languages: English
• ISSNs: 0892-7022

Abstract

Abstract: All-atom molecular dynamics simulations have been performed on cimetidine in the presence of a palmitoyloleoylphosphatidylcholine (POPC) bilayer. The free energy profile of a single cimetidine molecule passing across POPC bilayer displays a minimum at the interface of bilayer and water. Ten cimetidine molecules were inserted into POPC bilayer to obtain an 8 mol % drug model, and molecular dynamics results showed that cimetidine molecules reside at the polar region of POPC bilayer with sulphur atoms directing to the hydrophobic region. By comparing the one drug model with 8 mol % drug model, one can see that the central barrier to cross the membrane increases while the free energy in bulk water decreases, indicating that the ability of cimetidine passing across the POPC bilayer weakens at increased concentration. In addition, the free energy minimum shifts closer to the hydrophobic core. Our results indicate that with the increased drug concentration, it is more difficult for cimetidine to enter and pass across POPC bilayer.