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nanodisc

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Lipoproteins are protein-lipid particles which circulate in the blood collecting cholesterol, fatty acids, and lipids. Low levels of one such lipoprotein particle, called high-density lipoprotein (HDL) or "good cholesterol", has been implicated in the increased risk of coronary heart disease. The ability of lipoproteins to transport lipid and cholesterol through the blood is amazing since these types of particles are not generally soluble in blood plasma. However, when HDLs assemble, proteins wrap themselves around the lipids and cholesterol, shielding the lipid tails from the aqueous environment. Native HDL exhibit a variety of shapes and sizes, for example forming a discoidal particle. Conventional high-resolution imaging techniques, such as NMR and X-ray crystallography, cannot resolve how lipid and cholesterol are being accommodated by HDL, but the assembly and geometry of HDL discs can be captured using computer simulations. Unfortunately, the long time scales required for HDL assembly was a major stumbling block. Now a new simulation method, coarse-grained modeling in conjunction with the molecular dynamics program NAMD, has permitted the simulation of HDL assembly as recently reported. The simulations show that lipids quickly aggregate into a bilayer from their initial spherical "micelle" shape and that the two proteins subsequently attach to either side forming a belt surrounding the lipid core. For more information see HDL & nanodisc and coarse-grained modeling.