Study of lipid raft domains using computer simulation techniques



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The cholesterol condensing effect in DOPC bilayer was investigated via atomistic molecular dynamics (MD) simulation. The calculated partial-specific areas of lipids in DOPC/cholesterol lipid bilayer clearly show the condensing effect of cholesterol. The results showed that the total area of a PC/cholesterol bilayer is primarily determined by the molecular packing in the cholesterol sterol ring region. An alternative analysis of area per molecule within this region is proposed, which takes into account the cholesterol tilt angle and the practical incompressibility of cholesterol sterol rings. The new calculation shows that the majority of the area lost due to the cholesterol condensing effect is taken from PC molecules. MD simulation was also used to study the interactions between DAG, POPC, and cholesterol. Our results show that both DAG and cholesterol produce some very similar effects in POPC bilayers: increasing acyl chain order and bilayer thickness, reducing volume-per-lipid, and decreasing lateral diffusion of molecules. More significantly, DAG also produces a strong “condensing effect” in PC bilayers. In comparison, cholesterol is more effective than DAG in producing the above effects. Interestingly, our simulations also show that the largest spacing usually occurs between the first and the second nearest-neighbor PC headgroups from a DAG due to the umbrella effect. In another studies, the docking of PKCα-C1 and PKCβ-C2 domains to POPC/POPS/POG lipid bilayers were investigated using MD simulation. In the systems that contain PKCα-C1 domain, the domain only docks to a lipid bilayer that contains POG. This docking is accommodated with significant conformational changes in the PKCα-C1 domain structure. The docking of PKCα-C1 domain to lipid bilayers containing POG shows a high specificity of PKCα-C1 domain toward diacylglycerol. On the other hand, the PKCβ-C2 domain adapts a parallel configuration when it docks to the lipid bilayer in the absence of POG; however, at the presence of POG, it adapts a perpendicular configuration. Furthermore, PKCβ-C2 domain shows no significant conformational change during the docking, which agrees with the experimental studies.