The plasma apolipoproteins are a diverse group of proteins responsible for many functions in lipid metabolism. The apolipoproteins maintain lipoprotein particle structure, act as cofactors forenzymes, and are the ligands for receptors involved in the cellulartargeting of lipoprotein particles. Apolipoprotein A-I (28kD, 243AA) is the major protein component (70%) of plasma high density lipoprotein (HDL) particles [47, 48]. It is a potent activatorof the enzyme lecithin cholesterol acyl transferase (LCAT), a keyenzyme in the metabolism of cholesterol. Apolipoprotein A-I (apoA-I) does not assume a stable 3D structure in solution.In thepresence of phospholipid dispersions, apo A-I binds to the lipidsurfaces, markedly increases in ff-helical structure, and becomesstabilized [49, 50]. However, no 3D structure of apo A-I has beenexperimentally determined due to the difficulty of crystalization.The study of reconstituted HDL (rHDL) particles prepared bythe sodium cholate dialysis method [51] suggests the formation ofdiscoidal micelles [52] containing two or three apo A-I molecules,each of which contributes up to 8 amphipathic ff-helices to forma ring around the lipid bilayer. Our goal is to predict the 3D structure of apo A-I in a lipid environment, i.e. the discoidal formation of rHDL. The size of therHDL system is 15,000 to 20,000 atoms (not including waters around the rHDL), and its simulation requires a large amount oftime. We have recently finished predicting the secondary structure of apo A-I and assembling the ring-like structure of two apo A-I molecules. Our next goal is to build the entire discoidal system with apo A-I's, lipids, and water.
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