Molecular Dynamics Simulations on Discoidal HDL Particles Suggest a Mechanism for Rotation in the Apo A-I Belt Model》.pdfVIP

wB doi:10.1016/S0022-2836(02)01143-9 available online at on J. Mol. Biol. (2002) 324, 703–721 Molecular Dynamics Simulations on Discoidal HDL Particles Suggest a Mechanism for Rotation in the Apo A-I Belt Model 1 1,2 1* Anthony E. Klon , Jere P. Segrest and Stephen C. Harvey 1Department of Biochemistry Apolipoprotein A-I (apo A-I) is the major protein component of high- and Molecular Genetics density lipoprotein (HDL) particles. Elevated levels of HDL in the blood- The University of Alabama stream have been shown to correlate strongly with a reduced risk factor at Birmingham for atherosclerosis. Molecular dynamics simulations have been carried 1918 University Blvd out on three separate model discoidal high-density lipoprotein particles 552 Basic Health Sciences Bldg (HDL) containing two monomers of apo A-I and 160 molecules of palmi- Birmingham, AL 35294-0005 toyloleoylphosphatidylcholine (POPC), to a time-scale of 1 ns. The starting USA structures were on the basis of previously published molecular belt 2 models of HDL consisting of the lipid-binding C-terminal domain (resi- Department of Medicine dues 44–243) wrapped around the circumference of a discoidal HDL University of Alabama particle. Subtle changes between two of the starting structures resulted in at Birmingham, Birmingham significantly different behavior during the course of the simulation