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.
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.
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, United States.
Binwu
B
Zhao
Laboratory of Physical Chemistry & Colloid Science, Wageningen University, NL, Wageningen, The Netherlands.
Martien A
0000-0001-6880-7861
MA
Cohen Stuart
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, United States.
Carol K
0000-0002-7425-587X
CK
Hall
D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D000072417:Protein Domains; D017510:Protein Folding; D058767:Protein Unfolding; D047011:Silk / Q000737:chemistry* / Q000648:ultrastructure*
D010455:Peptides; D047011:Silk