title: Free energy landscape and multiple folding pathways of an H-type RNA pseudoknot.
abstract: How RNA sequences fold to specific tertiary structures is one of the key problems for understanding their dynamics and functions. Here, we study the folding process of an H-type RNA pseudoknot by performing a large-scale all-atom MD simulation and bias-exchange metadynamics. The folding free energy landscapes are obtained and several folding intermediates are identified. It is suggested that the folding occurs via multiple mechanisms, including a step-wise mechanism starting either from the first helix or the second, and a cooperative mechanism with both helices forming simultaneously. Despite of the multiple mechanism nature, the ensemble folding kinetics estimated from a Markov state model is single-exponential. It is also found that the correlation between folding and binding of metal ions is significant, and the bound ions mediate long-range interactions in the intermediate structures. Non-native interactions are found to be dominant in the unfolded state and also present in some intermediates, possibly hinder the folding process of the RNA.
authors.affiliation: Collaborative Innovation Center of Advanced Microstructures and Department of Physics, Nanjing University, Nanjing 210093, China; Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Institute of Biophysics, Dezhou University, Dezhou 253023, China.
authors.forename: Yunqiang
authors.initials: Y
authors.lastname: Bian
authors.affiliation: Collaborative Innovation Center of Advanced Microstructures and Department of Physics, Nanjing University, Nanjing 210093, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Collaborative Innovation Center of Advanced Microstructures and Department of Physics, Nanjing University, Nanjing 210093, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Institute of Biophysics, Dezhou University, Dezhou 253023, China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Collaborative Innovation Center of Advanced Microstructures and Department of Physics, Nanjing University, Nanjing 210093, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000235:genetics*; D013816:Thermodynamics
chemical_list: D012313:RNA