Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.566329
Title: Modelling the kinetics of amyloid fibril nucleation
Author: Cabriolu, Raffaela
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2012
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Abstract:
A kinetic theory has been developed within the framework of preexisting nucleation theory and applied, for the first time, to investigate the one-step formation of amyloid fibrils. Atomistic Nucleation Theory (ANT) for fibrils, in particular, has been successfully applied to model real peptides and proteins, in order to investigate at the molecular level the nucleation of amyloid fibrils from a homogeneous solution. Kinetic parameters predicted by the theory, such as the nucleation rates, have been compared successfully to the results of experiments. The present theoretical study has shown that variations in solubility are the primary origin of the changes in the nucleation rates between a protein and its point-mutations. The same ANT approach allows the analysis of the fibril size distribution, whose results, once again, are consistent with experimental observations. In the last stage of the investigation, computer simulations have been carried out to test selected assumptions underlying the theory. For the first time, the nucleation of strongly anisotropic systems has been investigated using kinetic Monte Carlo (KMC) simulations. Novel and unexpected features, never discussed before in either experiments or simulations studies, have been revealed by the simulations. Although obtained within the study of amyloid fibrils nucleation, these last results are of general validity, providing useful insight on the nucleation of all systems whose molecules interact via strongly anisotropic forces.
Supervisor: Auer, S. ; Kashchiev, D. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.566329  DOI: Not available
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