James C. Phillips, Willy Wriggers, Zhigang Li, Ana Jonas, and Klaus Schulten. Predicting the structure of apolipoprotein A-I in reconstituted high density lipoprotein disks. Biophysical Journal, 73:2337-2346, 1997.
In reconstituted high density lipoproteins, apolipoprotein A-I and phosphatydylcholines combine to form disks in which the amphipathic alpha-helices of apolipoprotein A-I bind to the edge of a lipid bilayer core, shielding the hydrophic lipid tails from the aqueous environment. We have employed experimental data, sequence analysis, and molecular modeling to construct an atomic model of such a reconstituted high density lipoproteins disk consisting of two apolipoprotein A-I proteins and 160 palmitoyloleoyl-phosphatidylcholine lipids. The initial globular domain (1-47) of apolipoprotein A-I was excluded from the model, which was hydrated with an 8 Å shell of water molecules. Molecular dynamics and simulated annealing were used to test the stability of the model. Both head-to-tail and head-to-head forms of reconstituted high density lipoproteins were simulated. In our simulations the protein contained and adhered to the lipid bilayer while providing good coverage of the lipid tails.
