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 β-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. © 2013 a Beccara et al.
CITATION STYLE
a Beccara, S., Škrbić, T., Covino, R., Micheletti, C., & Faccioli, P. (2013). Folding Pathways of a Knotted Protein with a Realistic Atomistic Force Field. PLoS Computational Biology, 9(3). https://doi.org/10.1371/journal.pcbi.1003002
Mendeley helps you to discover research relevant for your work.