Coarse-Grained Molecular Dynamics Simulation Approach to High-Density Lipoprotein-Mimetics Modeling

High-density lipoprotein (HDL) is an endogenous biological molecule with high heterogeneity, playing critical roles in several biological events including anti-inflammation and lipid homeostasis. However, it is difficult to uncover the detailed structural and biological function of each HDL component, mainly due to the heterogeneity of HDL induced by multiple compositions and HDL-associated proteins. To overcome heterogeneous characteristics of HDL, reconstituted HDL (rHDL) form has been presented to synthesize simplified form of HDL with major components in HDL, such as apolipoprotein A1 (apoA1), phospholipids (PL), and free cholesterol (FC). Recent developments in microfluidics have allowed us to produce more homogeneous HDL-mimetic nanoparticles with higher reproducibility. In addition, computational approaches have been introduced to conduct structural analysis of nanoparticles along with the development of computational methods. we introduce a computational strategy of molecular dynamic (MD) simulation with experimental correlations. Coarse grained (CG) MD simulation enables the detailed prediction of the HDL-mimetic nanoparticle’s structure, and binding structure of HDL with a major HDL associated proteins (HAPs), paraoxonase1 (PON1), while the microfluidic platform leads compositionally homogeneous nanoparticle synthesis to validate computational results. Our approach provides an insight to precisely analyze the compositionally and functionally heterogenous HDL and can be applied to elucidate the detailed binding mechanism of other associated proteins on well-defined HDL.

Date

2019-11-12

Resource Type

Text

Resource Subtype

Dissertation

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