Gene

Intramolecular force

Engineering

Chemical physics

Biology

Materials science

Metastability

Native state

Amyloid (mycology)

Polymorphism (computer science)

Folding (DSP implementation)

Biochemistry

Protein folding

Molecule

Inorganic chemistry

Intermolecular force

Stereochemistry

Organic chemistry

Ribbon

Genotype

Composite material

Crystallography

Chemistry

Contact order

Biophysics

Energy landscape

Electrical engineering

Angewandte Chemie International Edition

Protein folding involves a large number of steps and conformations in which the folding protein samples different thermodynamic states characterized by local minima. Kinetically trapped on- or off-pathway intermediates are metastable folding intermediates towards the lowest absolute energy minima, which have been postulated to be the natively folded state where intramolecular interactions dominate, and the amyloid state where intermolecular interactions dominate. However, this view largely neglects the rich polymorphism found within amyloid species. We review the protein folding energy landscape in view of recent findings identifying specific transition routes among different amyloid polymorphs. Observed transitions such as twisted ribbon→crystal or helical ribbon→nanotube, and forbidden transitions such helical ribbon↛crystal, are discussed and positioned within the protein folding and aggregation energy landscape. Finally, amyloid crystals are identified as the ground state of the protein folding and aggregation energy landscape.

Amyloid Polymorphism in the Protein Folding and Aggregation Energy Landscape