(104d) A Coarse Grained Model of Inhibitors to Scavenger Receptor Uptake to LDL
- Conference: AIChE Annual Meeting
- Year: 2011
- Proceeding: 2011 Annual Meeting
- Group: Computational Molecular Science and Engineering Forum
- Time: Monday, October 17, 2011 - 1:30pm-1:50pm
The buildup and oxidation of low-density lipoproteins (LDL) in the walls of arterial blood vessels results in atherosclerotic lesions and arterial damage. The immune response of this arterial damage is to recruit macrophages expressing scavenger receptors specific for the uptake of oxidized LDL. The result is the formation of foam cells and fatty streaks, the first signs of atherosclerotic plaques. One possible method to combat the formation of atherosclerotic plaques is through the use of inhibitors which prevent the uptake of oxidized LDL by the scavenger receptors. Recently, Tian et al. 2004  developed a class of molecules termed amphiphilic scorpion-like macromolecules (AScM) comprised of a mucic acid head group with attached aliphatic chains and a long polyethylene glycol (PEG) tail used specifically to block uptake of oxidized LDL by scavenger receptors. In this work, we use computational simulations to explore the structure and interactions of AscM micelles with the specific scavenger receptor – scavenger receptor A (SR-A) in order to shed light on an optimal inhibitor of oxidized LDL uptake.
In our simulations, we use a coarse-grained model based on the MARTINI force field  to describe the AScM molecules as well as the collagenous portion of SR-A where binding is assumed to take place . As the interaction of oxidized LDL is thought to be mediated by electrostatic interactions, we vary the number (0, 1, or 2) of carboxylate groups at different positions on the AScM (near the mucic acid head or at the PEG tail) to determine the effect on both AScM micellation (which it though necessary for SR-A binding) and AScM association with SR-A to determine the best inhibitor.
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