Multidimensional View of Amyloid Fibril Nucleation in Atomistic Detail
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By extended atomistic simulations in explicit solvent and bias-exchange metadynamics, we study the aggregation process of 18 chains of the C-terminal segment of amyloid-beta, an intrinsically disordered protein involved in Alzheimer's disease and prone to ...
In this article we review a set of methods for exploring the space of a set of collective variables, and to reconstruct the associated Landau free energy in presence of metastabilities: Temperature Accelerated Molecular Dynamics (TAMD), its extension, Temp ...
It has been more than a century since the first evidence linking the process of amyloid formation to the pathogenesis of Alzheimer's disease. During the last three decades in particular, increasing evidence from various sources (pathology, genetics, cell c ...
Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease share common mechanisms characterized by protein misfolding and aggregation, including formation of plaques or inclusion bodies. The rapid growing number o ...
The doppel (Dpl) and prion (PrP) proteins share a very similar fold (three helices and two short beta-strands), while they differ significantly in sequence (only 25% homologous) and in disease-related beta-rich conformations that occur for PrP only. In a p ...
The distinct conformational dependence of chemical shifts caused by R-helices and β-sheets renders NMR chemical shift analysis a powerful tool for the structural determination of proteins. However, the time scale of NMR experiments can make a secondary str ...
Molecular probes for selective Identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying cerebral amyloidoses. Here we report the chemical design of pentameric thiophene derivatives, denoted lu ...
The aggregation of proteins is central to many aspects of daily life, including food processing, blood coagulation, eye cataract formation disease and prion-related neurodegenerative infections[1–5]. However, the physical mechanisms responsible for amyloid ...
Molecular dynamics (MD) simulations have increasingly contributed to the understanding of biomolecular processes, allowing for predictions of thermodynamic and structural properties. Unfortunately, the holy grail of protein structure prediction was soon fo ...
Elucidating the fine structure of amyloid fibrils as well as understanding their processes of nucleation and growth remains a difficult yet essential challenge, directly linked to our current poor insight into protein misfolding and aggregation diseases. H ...