Paper Citing NAMD - Abstract
Segrest, Jere P.; Jones, Martin K.; Catte, Andrea; Thirumuruganandham, Saravana P.
Validation of previous computer models and MD simulations of discoidal HDL by a recent crystal structure of apoA-I
JOURNAL OF LIPID RESEARCH, 53:1851-1863, SEP 2012
HDL is a population of apoA-I-containing particles inversely correlated with heart disease. Because HDL is a soft form of matter deformable by thermal fluctuations, structure determination has been difficult. Here, we compare the recently published crystal structure of lipid-free (Delta 185-243) apoA-I with apoA-I structure from models and molecular dynamics (MD) simulations of discoidal HDL. These analyses validate four of our previous structural findings for apoA-I: i) a baseline double belt diameter of 105 angstrom; ii) central alpha helixes with an 11/3 pitch; iii) a "presentation tunnel" gap between pairwise helix 5 repeats hypothesized to move acyl chains and unesterified cholesterol from the lipid bilayer to the active sites of LCAT; and iv) interchain salt bridges hypothesized to stabilize the LL5/5 chain registry. These analyses are also consistent with our finding that multiple salt bridge-forming residues in the N-terminus of apoA-I render that conserved domain "sticky." Additionally, our crystal MD comparisons led to two new hypotheses: i) the interchain leucine-zippers previously reported between the pair-wise helix 5 repeats drive lipid-free apoA-I registration; ii) lipidation induces rotations of helix 5 to allow formation of interchain salt bridges, creating the LCAT presentation tunnel and "zip-locking" apoA-I into its full LL5/5 registration.-Segrest, J. P., M. K. Jones, A. Catte, and S. P. Thirumuruganandham. Validation of previous computer models and MD simulations of discoidal HDL by a recent crystal structure of apoA-I. J. Lipid Res. 2012. 53: 1851-1863.
