The amyloid conversion is a massive detrimental modification affecting several proteins upon specific physical or chemical stimuli characterizing a plethora of diseases. In many cases, the amyloidogenic stimuli induce specific structural features to the protein conferring the propensity to misfold and form amyloid deposits. The investigation of mutants, structurally similar to their native isoform but inherently prone to amyloid conversion, may be a viable strategy to elucidate the structural features connected with amyloidogenesis. In this paper, we present a computational protocol based on the combination of molecular dynamics (MD) and grid-based approaches suited for the pairwise comparison of closely related protein structures. This method was applied on the cellular prion protein (PrP(C) ) as a case study and, in particular, addressed to the quali/quantification of the structural features conferred by either E200K mutations and treatment with CaCl2 , both able to induce the scrapie conversion of PrP. Several schemes of comparison were developed and applied to this case study, and made up suitable of application to other protein systems. At this purpose an in-hose python codes has been implemented that, together with the parallelization of the GRID force fields program, will spread the applicability of the proposed computational procedure. This article is protected by copyright. All rights reserved.

Investigation of the molecular similarity in closely related protein systems: The PrP case study

STORCHI, LORIANO;PACIOTTI, ROBERTO;RE, Nazzareno;MARRONE, Alessandro
2015-01-01

Abstract

The amyloid conversion is a massive detrimental modification affecting several proteins upon specific physical or chemical stimuli characterizing a plethora of diseases. In many cases, the amyloidogenic stimuli induce specific structural features to the protein conferring the propensity to misfold and form amyloid deposits. The investigation of mutants, structurally similar to their native isoform but inherently prone to amyloid conversion, may be a viable strategy to elucidate the structural features connected with amyloidogenesis. In this paper, we present a computational protocol based on the combination of molecular dynamics (MD) and grid-based approaches suited for the pairwise comparison of closely related protein structures. This method was applied on the cellular prion protein (PrP(C) ) as a case study and, in particular, addressed to the quali/quantification of the structural features conferred by either E200K mutations and treatment with CaCl2 , both able to induce the scrapie conversion of PrP. Several schemes of comparison were developed and applied to this case study, and made up suitable of application to other protein systems. At this purpose an in-hose python codes has been implemented that, together with the parallelization of the GRID force fields program, will spread the applicability of the proposed computational procedure. This article is protected by copyright. All rights reserved.
File in questo prodotto:
File Dimensione Formato  
Storchi_et_al-2015-Proteins-_Structure,_Function,_and_Bioinformatics.pdf

Solo gestori archivio

Tipologia: PDF editoriale
Dimensione 789.85 kB
Formato Adobe PDF
789.85 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/639690
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 15
  • ???jsp.display-item.citation.isi??? 15
social impact