Navigating in foldonia: Using accelerated molecular dynamics to explore stability, unfolding and self-healing of the ß-solenoid structure formed by a silk-like polypeptide.
PLoS Comput Biol
; 13(3): e1005446, 2017 03.
Article
em En
| MEDLINE
| ID: mdl-28329017
ABSTRACT
The ß 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 ß 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 ß roll configuration. Our study shows that a molecule in a stack of two ß 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 ß roll structure of the molecule on top by strengthening the hydrogen bonds in the layer that it contacts. Vertical hydrogen bonds within the ß roll structure are considerably weaker than lateral hydrogen bonds, signifying the importance of lateral hydrogen bonds in stabilizing the ß roll structure. Finally, an intermediate structure was found containing a ß hairpin and an anti-parallel ß sheet consisting of strands from the top and bottom molecules, revealing the self-healing ability of the ß roll stack.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Dobramento de Proteína
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Seda
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Simulação de Dinâmica Molecular
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Modelos Químicos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article