title: Assembly of the five-way junction in the ribosomal small subunit using hybrid MD-Gō simulations.
abstract: Assembly of the bacterial ribosomal small subunit (SSU) begins with the folding of the five-way junction upon interaction with the primary binding protein S4. This complex contains the largest contiguous molecular signature, which is a conserved feature in all bacterial 16S rRNAs. In a previous study, we used all-atom molecular dynamics simulations to demonstrate that the co-evolving signature in the N-terminus of S4 is intrinsically disordered and capable of accelerating the binding process through a fly casting mechanism. In this paper, comparisons between the all-atom MD simulations and FRET experiments identify multiple metastable conformations of the naked five-way junction without the presence of S4. Furthermore, we capture the simultaneous folding and binding of the five-way junction and r-protein S4 by use of a structure-based Gō potential implemented within the framework of the all-atom molecular dynamics CHARMM force field. Different folding pathways are observed for the refolding of the five-way junction upon partial binding of S4. Our simulations illustrate the complex nature of RNA folding in the presence of a protein binding partner and provide insight into the role of population shift and the induced fit mechanisms in the protein:RNA folding and binding process.
authors.affiliation: Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Eargle
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lai
authors.forename: Hajin
authors.initials: H
authors.lastname: Kim
authors.forename: Sanjaya
authors.initials: S
authors.lastname: Abeysirigunawardena
authors.forename: Megan
authors.initials: M
authors.lastname: Mayerle
authors.forename: Sarah
authors.initials: S
authors.lastname: Woodson
authors.forename: Taekjip
authors.initials: T
authors.lastname: Ha
authors.forename: Zaida
authors.initials: Z
authors.lastname: Luthey-Schulten
mesh_terms: D031541:Fluorescence Resonance Energy Transfer; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D021122:Protein Subunits / Q000737:chemistry*; D012336:RNA, Ribosomal, 16S / Q000737:chemistry*
chemical_list: D021122:Protein Subunits; D012336:RNA, Ribosomal, 16S