title: Coarse-Grained Modeling of Peptide Docking Associated with Large Conformation Transitions of the Binding Protein: Troponin I Fragment-Troponin C System.
abstract: Most of the current docking procedures are focused on fine conformational adjustments of assembled complexes and fail to reproduce large-scale protein motion. In this paper, we test a new modeling approach developed to address this problem. CABS-dock is a versatile and efficient tool for modeling the structure, dynamics and interactions of protein complexes. The docking protocol employs a coarse-grained representation of proteins, a simplified model of interactions and advanced protocols for conformational sampling. CABS-dock is one of the very few tools that allow unrestrained docking with large conformational freedom of the receptor. In an example application we modeled the process of complex assembly between two proteins: Troponin C (TnC) and the N-terminal helix of Troponin I (TnI N-helix), which occurs in vivo during muscle contraction. Docking simulations illustrated how the TnC molecule undergoes significant conformational transition on complex formation, a phenomenon that can be modeled only when protein flexibility is properly accounted for. This way our procedure opens up a new possibility for studying mechanisms of protein complex assembly, which may be a supporting tool for rational drug design.
authors.affiliation: Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland. jwabik@chem.uw.edu.pl.
authors.forename: Jacek
authors.initials: J
authors.lastname: Wabik
authors.affiliation: Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland. mkurc@chem.uw.edu.pl.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kurcinski
authors.affiliation: Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland. kolinski@chem.uw.edu.pl.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kolinski
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009119:Muscle Contraction; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D019209:Troponin C / Q000737:chemistry* / Q000378:metabolism; D019210:Troponin I / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D010455:Peptides; D019209:Troponin C; D019210:Troponin I
keywords: coarse-grained modeling; flexible docking; molecular mechanisms; protein docking