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

作者：Zhao Binwu; Stuart Martien A Cohen; Hall Carol K

来源：PLoS Computational Biology, 2017, 13(3): e1005446.

DOI：10.1371/journal.pcbi.1005446

The beta 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 beta 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 beta roll configuration. Our study shows that a molecule in a stack of two beta 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 beta roll structure of the molecule on top by strengthening the hydrogen bonds in the layer that it contacts. Vertical hydrogen bonds within the beta roll structure are considerably weaker than lateral hydrogen bonds, signifying the importance of lateral hydrogen bonds in stabilizing the beta roll structure. Finally, an intermediate structure was found containing a beta hairpin and an anti-parallel beta sheet consisting of strands from the top and bottom molecules, revealing the self-healing ability of the beta roll stack.

• 出版日期2017-3