TCB Publications - Abstract

Amy Y. Shih, Peter L. Freddolino, Anton Arkhipov, Stephen G. Sligar, and Klaus Schulten. Molecular modeling of the structural properties and formation of high-density lipoprotein particles. In Scott Feller, editor, Current Topics in Membranes: Computational Modeling of Membrane Bilayers, chapter 11, pp. 313-342. Elsevier, 2008.

SHIH2008 Even though high density lipoproteins (HDL) have been studied for decades, and implications of HDL for coronary heart disease are well documented, the structure of apo A-I and the transitions from lipid-free/poor to nascent discoidal to mature spherical HDL particles are not well characterized. The large structural changes in HDL particles along with the plasticity of the apo A-I protein have been difficult to study by traditional experimental high-resolution structural techniques such as X-ray crystallography and NMR. Any structure arising from such techniques would be static by nature and would not reveal in a dynamical sense the assembly and transformations of HDL particles. Molecular dynamics simulations, on the other hand, allow one to image the dynamic assembly and transformation of HDL. In this review, the simulation methods used to simulate lipoprotein particles, namely all-atom and coarse-grained molecular dynamics, will be introduced along with small-angle X-ray scattering, an experimental method that resolves the shape HDL particles. Recent progress towards determining computationally and experimentally structure and assembly of discoidal HDL and idealized nanodisc particles will then be presented.

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