Affiliation:
1. Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
Abstract
Amyloid formation is a hallmark of various neurodegenerative disorders. In this contribution, energy landscapes are explored for various hexapeptides that are known to form amyloids. Heat capacity (CV) analysis at low temperature for these hexapeptides reveals that the low energy structures contributing to the first heat capacity feature above a threshold temperature exhibit a variety of backbone conformations for amyloid-forming monomers. The corresponding control sequences do not exhibit such structural polymorphism, as diagnosed via end-to-end distance and a dihedral angle defined for the monomer. A similar heat capacity analysis for dimer conformations obtained using basin-hopping global optimisation shows clear features in end-to-end distance versus dihedral correlation plots, where amyloid-forming sequences exhibit a preference for larger end-to-end distances and larger positive dihedrals. These results hold true for sequences taken from tau, amylin, insulin A chain, a de novo designed peptide, and various control sequences. While there is a little overall correlation between the aggregation propensity and the temperature at which the low-temperature CV feature occurs, further analysis suggests that the amyloid-forming sequences exhibit the key CV feature at a lower temperature compared to control sequences derived from the same protein.
Funder
Engineering and Physical Sciences Research Council
Cambridge Commonwealth, European and International Trust
Allen, Meek and Read Fund
Santander fund, St Edmund’s College, University of Cambridge
Trinity-Henry Barlow Honorary Award
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
1 articles.
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