Concentration effect of cimetidine with POPC bilayer: a molecular dynamics simulation study

Abstract

a tianjin Key laboratory of Molecular Design and Drug Discovery, tianjin institute of Pharmaceutical research, tianjin, P.r. china; b State Key laboratory of Drug Delivery technology and Pharmacokinetics, tianjin institute of Pharmaceutical research, tianjin, P.r. china 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.

Synergistic Effects of IMX-104 Components in Membrane Absorption: A Computational Study

“…Our previous work suggested that TNT molecules previously entering the membrane will promote the permeability of the latter molecules in the membrane, and the VDW interactions between TNT molecules play the main role in their attraction and clustering . Wang et al reported that 8 mol % of cimetidine would lead to a decrease in the ability of subsequent cimetidine molecules across the membrane, which was attributed to the insignificant interactions between cimetidine molecules . Therefore, we calculated the VDW energy between the explosive molecules during their membrane adsorption process in a mixture system.…”

“… 22 Wang et al reported that 8 mol % of cimetidine would lead to a decrease in the ability of subsequent cimetidine molecules across the membrane, which was attributed to the insignificant interactions between cimetidine molecules. 49 Therefore, we calculated the VDW energy between the explosive molecules during their membrane adsorption process in a mixture system. It can be seen from Figure 6 that the VDW energy between RDX molecules (VMD-RR) is very weak and quickly decreased to almost zero, even showing repulsion to each other.…”

Collective absorption of 2,4,6-trinitrotoluene into lipid membranes and its effects on bilayer properties. A computational study

“…Furthermore, in the TNT-40 system, the more pronounced changes in the free energy profile might be related to the formation of the membrane-spanning aggregate, in which some TNT molecules could stably reside in the hydrophobic core, and further affect the local barrier of the bilayer center. In the recent simulation, Wang et al 49 reported the effect of concentration on the adsorption and transmembrane process of cimetidine. In detail, 8 mol% of cimetidine would lead to a decrease in the ability of subsequent cimetidine molecules across the membrane and a decline of passive permeability, which was attributed to the insignificant interactions between cimetidine molecules.…”