The proposed program project will exam structure-function relationships in model high density lipoprotein particles (HDLs) in a series of computer simulations which will need state -of- the- art computer hardware. The foundation for this work is a set of molecular dynamics (MD) simulations that were carried out on model membranes. Basic protocols and the parameters appropriate for lipid MD simulations have been established. More recently, MD simulations on model HDL particles have begun. The impact of computer hardware on these simulations is apparent. It is stated that simulation on these models requires four months on their in-house hardware, a four processor SGI Origin system. A larger simulation has been carried out on a dedicated 32 processor Beowulf cluster at the University of Illinois. They propose to carry out simulations on several belt models, including those described above and other mutations. These are to be done for HDL particles containing a variety of lipids (DMPC, DPPC, POPC). Several control simulations will also be done, both on belt models and on competing picket fence models. They estimate that these initial simulations would require 1-2 years of CPU time on the proposed 64 processor Beowulf cluster. A wide variety of structural problems on other lipoprotein particles would consume the cluster for the remainder of the proposed grant period. Instrumentation for the Program Project is centralized in this Core.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL034343-19
Application #
7083529
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
19
Fiscal Year
2005
Total Cost
$283,687
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
White, C Roger; Giordano, Samantha; Anantharamaiah, G M (2016) High-density lipoprotein, mitochondrial dysfunction and cell survival mechanisms. Chem Phys Lipids 199:161-169
Namiri-Kalantari, Ryan; Gao, Feng; Chattopadhyay, Arnab et al. (2015) The dual nature of HDL: Anti-Inflammatory and pro-Inflammatory. Biofactors 41:153-9
White, C Roger; Goldberg, Dennis I; Anantharamaiah, G M (2015) Recent developments in modulating atherogenic lipoproteins. Curr Opin Lipidol 26:369-75
Datta, Geeta; Kramer, Philip A; Johnson, Michelle S et al. (2015) Bioenergetic programming of macrophages by the apolipoprotein A-I mimetic peptide 4F. Biochem J 467:517-27
Navab, Mohamad; Chattopadhyay, Arnab; Hough, Greg et al. (2015) Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis. J Lipid Res 56:871-87
Segrest, Jere P; Jones, Martin K; Catte, Andrea et al. (2015) A robust all-atom model for LCAT generated by homology modeling. J Lipid Res 56:620-34
Guo, Lilu; Chen, Zhongyi; Amarnath, Venkataraman et al. (2015) Isolevuglandin-type lipid aldehydes induce the inflammatory response of macrophages by modifying phosphatidylethanolamines and activating the receptor for advanced glycation endproducts. Antioxid Redox Signal 22:1633-45
Segrest, Jere P; Jones, Martin K; Catte, Andrea et al. (2015) Surface Density-Induced Pleating of a Lipid Monolayer Drives Nascent High-Density Lipoprotein Assembly. Structure 23:1214-26
Segrest, Jere P; Jones, Martin K; Shao, Baohai et al. (2014) An experimentally robust model of monomeric apolipoprotein A-I created from a chimera of two X-ray structures and molecular dynamics simulations. Biochemistry 53:7625-40
Sharifov, Oleg F; Xu, Xin; Gaggar, Amit et al. (2014) L-4F inhibits lipopolysaccharide-mediated activation of primary human neutrophils. Inflammation 37:1401-12

Showing the most recent 10 out of 197 publications