Exploring the candidates for a new protein folding -- cross-α amyloid -- in available protein databases

Amyloid fibrils are formed from the assembly of soluble proteins and are responsible for many diseases. They are known to have cross-β structure, where the fibril runs perpendicular to the β-sheets. A new type of tertiary structure formed from the aggregation of peptides in their α-helical form, in naturally occurring as well as synthetic peptides, termed as cross-α amyloid has been reported recently. We have studied the interactions responsible for the formation of these cross-α amyloids and proposed a model to determine the peptides that could form these structures. Eight such peptides obtained from the model have been shown to form cross-α structure using molecular dynamics simulations. The formation of a cross-α structure from eight copies of a randomly chosen peptide and its stability over a microsecond simulation has been demonstrated. A software named Cross-Alpha-Det has been developed which can determine from its secondary structure whether the protein can form a cross-α structure.