An insight of early PrP‐E200K aggregation by combined molecular dynamics/fragment molecular orbital approaches
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- Roberto Paciotti
- Department of Pharmacy Università “G d'Annunzio” di Chieti‐Pescara Chieti Italy
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- Loriano Storchi
- Department of Pharmacy Università “G d'Annunzio” di Chieti‐Pescara Chieti Italy
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- Alessandro Marrone
- Department of Pharmacy Università “G d'Annunzio” di Chieti‐Pescara Chieti Italy
説明
<jats:title>Abstract</jats:title><jats:p>Unveiling the events leading to the formation of prion particles is a nowadays challenge in the field of neurochemistry. Pathogenic mutants of prion protein (PrP) are characterized by both an intrinsic tendency to aggregation and scrapie conversion propensity. However, the question about a possible correlation between these two events lasts still unanswered. Here, a multilayered computational workflow was employed to investigate structure, stability, and molecular interaction properties of a dimer of PrP<jats:sup>C</jats:sup>‐E200K, a well‐known mutant of the PrP that represents a reduced model of early aggregates of this protein. Based on the combination of molecular dynamics and quantum mechanical approaches, this study provided for an in depth insight of PrP<jats:sup>C</jats:sup>‐E200K dimer in terms of residue‐residue interactions. Assembly hypotheses for the early aggregation of PrP<jats:sup>C</jats:sup>‐E200K are paved and compared with PrP<jats:sup>Sc</jats:sup> models reported in the literature to find a structural link between early and late (scrapie) aggregates of this protein.</jats:p>
収録刊行物
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- Proteins: Structure, Function, and Bioinformatics
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Proteins: Structure, Function, and Bioinformatics 87 (1), 51-61, 2018-11-16
Wiley
