We report on atomistic simulation of the folding of a natively-knotted protein, MJ0366, based on a realistic force field. To the best of our knowledge this is the first reported effort where a realistic force field is used to investigate the folding pathways of a protein with complex native topology. By using the dominant-reaction pathway scheme we collected about 30 successful folding trajectories for the 82-amino acid long trefoil-knotted protein. Despite the dissimilarity of their initial unfolded configuration, these trajectories reach the natively-knotted state through a remarkably similar succession of steps. In particular it is found that knotting occurs essentially through a threading mechanism, involving the passage of the C-terminal through an open region created by the formation of the native -sheet at an earlier stage. The dominance of the knotting by threading mechanism is not observed in MJ0366 folding simulations using simplified, native-centric models. This points to a previously underappreciated role of concerted amino acid interactions, including non-native ones, in aiding the appropriate order of contact formation to achieve knotting.

Faccioli, P., Michelett, C., Skrbic, T., Covino, S., A Beccara, S. (2013). Folding Pathways of a Knotted Protein with a Realistic Atomistic Force Field. PLOS COMPUTATIONAL BIOLOGY, 9(3) [10.1371/journal.pcbi.1003002].

Folding Pathways of a Knotted Protein with a Realistic Atomistic Force Field

Faccioli, Pietro;
2013

Abstract

We report on atomistic simulation of the folding of a natively-knotted protein, MJ0366, based on a realistic force field. To the best of our knowledge this is the first reported effort where a realistic force field is used to investigate the folding pathways of a protein with complex native topology. By using the dominant-reaction pathway scheme we collected about 30 successful folding trajectories for the 82-amino acid long trefoil-knotted protein. Despite the dissimilarity of their initial unfolded configuration, these trajectories reach the natively-knotted state through a remarkably similar succession of steps. In particular it is found that knotting occurs essentially through a threading mechanism, involving the passage of the C-terminal through an open region created by the formation of the native -sheet at an earlier stage. The dominance of the knotting by threading mechanism is not observed in MJ0366 folding simulations using simplified, native-centric models. This points to a previously underappreciated role of concerted amino acid interactions, including non-native ones, in aiding the appropriate order of contact formation to achieve knotting.
Articolo in rivista - Articolo scientifico
Molecular Biology
English
2013
9
3
e1003002
none
Faccioli, P., Michelett, C., Skrbic, T., Covino, S., A Beccara, S. (2013). Folding Pathways of a Knotted Protein with a Realistic Atomistic Force Field. PLOS COMPUTATIONAL BIOLOGY, 9(3) [10.1371/journal.pcbi.1003002].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/405570
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