Interactions of Fibrillar Proteins with Lipids: A Molecular Docking Insight
The aggregation of misfolded proteins into specific ordered aggregates, amyloid fibrils, associated with more than forty human diseases, currently attracts great research attention in biomedical and nanotechnological aspects. These aggregates and their oligomeric intermediates are thought to exert their toxic action predominantly at the level of cell membranes. In addition, membrane lipids were found in many amyloid deposits in vivo suggesting that lipid molecules are able to incorporate into fibril structure affecting their morphology and mechanical properties. However, the biological implications and structural prerequisites of fibril-lipid interactions still remain unclear. In the present study the molecular docking techniques was employed to explore the interactions between the amyloid fibrils and lipids in the model systems containing the fibrillar forms of lysozyme, insulin, Aβ (1-42) peptide and N-terminal (1-83) fragment of apolipoprotein A-I, as a protein component and cholesterol, cardiolipin or phosphatidylcholine as a lipid component. Using the PatchDock web server and BIOVIA Discovery Studio software, the structural peculiarities of fibril-lipid associates were uncovered. The van der Waals and alkyl/π-alkyl interactions were found to prevail in stabilization of all types of fibril-lipid complexes. The analysis of most energetically favorable docking positions revealed a preferable surface location of lipids and partial penetration of acyl chains of cardiolipin and phosphatidylcholine into fibril grooves.
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