Navigating in foldonia: Using accelerated molecular dynamics to explore stability, unfolding and self-healing of the β-solenoid structure formed by a silk-like polypeptide

• Published in: PLoS computational biology Vol. 13; no. 3; p. e1005446
• Main Authors: Zhao, Binwu, Cohen Stuart, Martien A, Hall, Carol K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2017; Public Library of Science (PLoS)
• Subjects: Biology and Life Sciences; Models, Chemical; Molecular Dynamics Simulation; Peptides - chemistry; Physical Chemistry and Soft Matter; Physical Sciences; Protein Conformation; Protein Domains; Protein Folding; Protein Unfolding; Silk - chemistry; Silk - ultrastructure
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1005446

The β roll molecules with sequence (GAGAGAGQ)10 stack via hydrogen bonding to form fibrils which have been themselves been used to make viral capsids of DNA strands, supramolecular nanotapes and pH-responsive gels. Accelerated molecular dynamics (aMD) simulations are used to investigate the unfolding of a stack of two β roll molecules, (GAGAGAGQ)10, to shed light on the folding mechanism by which silk-inspired polypeptides form fibrils and to identify the dominant forces that keep the silk-inspired polypeptide in a β roll configuration. Our study shows that a molecule in a stack of two β roll molecules unfolds in a step-wise fashion mainly from the C terminal. The bottom template is found to play an important role in stabilizing the β roll structure of the molecule on top by strengthening the hydrogen bonds in the layer that it contacts. Vertical hydrogen bonds within the β roll structure are considerably weaker than lateral hydrogen bonds, signifying the importance of lateral hydrogen bonds in stabilizing the β roll structure. Finally, an intermediate structure was found containing a β hairpin and an anti-parallel β sheet consisting of strands from the top and bottom molecules, revealing the self-healing ability of the β roll stack.