Abstract:
:The characterization of the structural dynamics of proteins, including those that present a substantial degree of disorder, is currently a major scientific challenge. These dynamics are biologically relevant and govern the majority of functional and pathological processes. We exploited a combination of enhanced molecular simulations of metadynamics and NMR measurements to study heterogeneous states of proteins and peptides. In this way, we determined the structural ensemble and free-energy landscape of the highly dynamic helix 1 of the prion protein (PrP-H1), whose misfolding and aggregation are intimately connected to a group of neurodegenerative disorders known as transmissible spongiform encephalopathies. Our combined approach allowed us to dissect the factors that govern the conformational states of PrP-H1 in solution, and the implications of these factors for prion protein misfolding and aggregation. The results underline the importance of adopting novel integrated approaches that take advantage of experiments and theory to achieve a comprehensive characterization of the structure and dynamics of biological macromolecules.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Camilloni C,Schaal D,Schweimer K,Schwarzinger S,De Simone Adoi
10.1016/j.bpj.2011.12.003subject
Has Abstractpub_date
2012-01-04 00:00:00pages
158-67issue
1eissn
0006-3495issn
1542-0086pii
S0006-3495(11)05368-9journal_volume
102pub_type
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