Assembly of the five-way junction in the ribosomal small subunit using hybrid MD-Gō simulations.
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The journal of physical chemistry. B, ISSN: 1520-5207, Vol: 116, Issue: 23, Page: 6819-31
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- Chemistry; Materials Science; Binding process; Binding proteins; Complex nature; Folding pathway; Force fields; Induced-fit mechanism; MD simulation; Molecular dynamics simulations; Molecular signatures; Protein binding partners; Refolding; RNA folding; Shift-and; Small subunits; Structure-based
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.