title: Conformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations.
abstract: GroEL is an ATP dependent molecular chaperone that promotes the folding of a large number of substrate proteins in E. coli. Large-scale conformational transitions occurring during the reaction cycle have been characterized from extensive crystallographic studies. However, the link between the observed conformations and the mechanisms involved in the allosteric response to ATP and the nucleotide-driven reaction cycle are not completely established. Here we describe extensive (in total long) unbiased molecular dynamics (MD) simulations that probe the response of GroEL subunits to ATP binding. We observe nucleotide dependent conformational transitions, and show with multiple 100 ns long simulations that the ligand-induced shift in the conformational populations are intrinsically coded in the structure-dynamics relationship of the protein subunit. Thus, these simulations reveal a stabilization of the equatorial domain upon nucleotide binding and a concomitant "opening" of the subunit, which reaches a conformation close to that observed in the crystal structure of the subunits within the ADP-bound oligomer. Moreover, we identify changes in a set of unique intrasubunit interactions potentially important for the conformational transition.
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Skjaerven
authors.forename: Barry
authors.initials: B
authors.lastname: Grant
authors.forename: Arturo
authors.initials: A
authors.lastname: Muga
authors.forename: Knut
authors.initials: K
authors.lastname: Teigen
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Reuter
authors.forename: Aurora
authors.initials: A
authors.lastname: Martinez
mesh_terms: D001665:Binding Sites; D018834:Chaperonin 60 / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018834:Chaperonin 60; D008024:Ligands; D009711:Nucleotides; D021122:Protein Subunits