title: Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model.
abstract: Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Dashuai
authors.initials: D
authors.lastname: Lv
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Cunxin
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Science, Yanshan University, Qinhuangdao 066004, China.
authors.forename: Jiguo
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000225:Adenine / Q000737:chemistry*; D002413:Cations, Divalent / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry; D008956:Models, Chemical; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D058928:Riboswitch
chemical_list: D002413:Cations, Divalent; D058928:Riboswitch; D008274:Magnesium; D000225:Adenine