High density lipoproteins (HDL) prevent the formation of plaques in arteries by transporting excess cholesterol from peripheral tissues to liver for excretion. Hence, elevated levels of HDL is vital in controlling the progression of cardiovascular diseases (CVD). Inspite of HDL's preventive role in CVD, very less is known about its structure and function. Recent chemical cross-linking and mass spectrometry studies revealed that the core structure of HDL is wrapped by three to five apoA-I proteins, which influence the binding of various metabolic enzymes like LCAT and CETP.1 A sophisticated model of HDL wrapped with four to five apoA-I chains is still missing in the literature, although some effort has been put forward to design the structure of HDL wrapped with smaller number of apoA-I chains.2 In the present work, we propose a model of HDL that resembles the experimentally measured composition of POPC, PPC, cholesterol, cholesteryl ester and triglyceride molecules. The self-assembled droplet from coarse-grained simulation was subsequently wrapped with four apoA-I chains (tetrafoil model) and reverse transformed. The lipid-protein interactions and the structural organization of lipids in HDL were analysed through multi-microsecond coarse-grained and united atom simulations. The model is validated by reproducing various experimentally determined properties, such as the density of HDL, apoA-I chemical cross links, diffusion coefficients of lipid fractions and order parameter of lipid acyl chains.1. Huang et al., Apolipoprotein A-I structural organization in high-density lipoproteins isolated from human. Plasma Nat. Struct. Mol. Biol.2011, 18 (4) 416-422.2. Vuorela et al., Role of Lipids in Spheroidal High Density Lipoproteins PLoS Comput. Biol.2010, 6, e1000964.