2013/02/08 by S. a Beccara, Beccara, Silvio a, Tatjana Škrbić +8 · 1 citation
Biochemistry, Genetics and Molecular Biology · Engineering · Physics and Astronomy · #Adhesion, Friction, and Surface Interactions #Biochemical and Structural Characterization #Biological Physics (physics.bio-ph) #Biomolecules (q-bio.BM) #FOS: Biological sciences #FOS: Physical sciences #Force Microscopy Techniques and Applications #Protein Structure and Dynamics #Soft Condensed Matter (cond-mat.soft)
paper · pdf · doi:10.48550/arxiv.1302.2003
openalex publication_date 2013/02/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
We report on atomistic simulation of the folding of a natively-knotted\nprotein, MJ0366, based on a realistic force field. To the best of our knowledge\nthis is the first reported effort where a realistic force field is used to\ninvestigate the folding pathways of a protein with complex native topology. By\nusing the dominant-reaction pathway scheme we collected about 30 successful\nfolding trajectories for the 82-amino acid long trefoil-knotted protein.\nDespite the dissimilarity of their initial unfolded configuration, these\ntrajectories reach the natively-knotted state through a remarkably similar\nsuccession of steps. In particular it is found that knotting occurs essentially\nthrough a threading mechanism, involving the passage of the C-terminal through\nan open region created by the formation of the native beta-sheet at an earlier\nstage. The dominance of the knotting by threading mechanism is not observed in\nMJ0366 folding simulations using simplified, native-centric models. This points\nto a previously underappreciated role of concerted amino acid interactions,\nincluding non-native ones, in aiding the appropriate order of contact formation\nto achieve knotting.\n