title: Inter-ring rotation of apolipoprotein A-I protein monomers for the double-belt model using biased molecular dynamics.
abstract: The double belt model for lipid-bound discoidal apolipoprotein A-I consists of two alpha-helical monomers bound about an unilamellar bilayer of lipids. Previous work, based on salt bridge calculations, has demonstrated that the L5/5 registration, Milano mutant, and Paris mutant are preferred conformations for apolipoprotein A-I. The salt bridge scoring indicated better energetic scoring in these alignments. The Paris (R151C) and Milano (R173C) mutants indicate a mode of change must be available. To find proper registration, one proposed change is a 'rotationally' independent circular motion of the two protein monomers about the lipid unilamellar bilayer core. Here, we present computational data for independent inter-ring rotation of the two alpha-helical monomers about the lipid unilamellar bilayer core. The simulations presented here support the existing double-belt model. We find the rotation of the two protein monomers is able to occur with biasing. We determine that a cysteine mutant at Glu107 as a possible target for future mutational studies. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling through dynamics has substantial biomedical implications.
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA. thomas.caulfield@chemistry.gatech.edu
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Caulfield
mesh_terms: D019943:Amino Acid Substitution; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D016632:Apolipoprotein A-I; D008051:Lipid Bilayers; D002784:Cholesterol