title: Folding pathways of a knotted protein with a realistic atomistic force field.
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 [Formula: see text]-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.
authors.affiliation: LISC, Bruno Kessler Foundation, Trento, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: a Beccara
authors.forename: Tatjana
authors.initials: T
authors.lastname: Škrbić
authors.forename: Roberto
authors.initials: R
authors.lastname: Covino
authors.forename: Cristian
authors.initials: C
authors.lastname: Micheletti
authors.forename: Pietro
authors.initials: P
authors.lastname: Faccioli
mesh_terms: D000465:Algorithms; D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism*; D019295:Computational Biology; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics
chemical_list: D019843:Archaeal Proteins
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