Modeling Loop Composition and Ion Concentration Effects in RNA Hairpin Folding Stability. 2020

Chenhan Zhao, and Dong Zhang, and Yangwei Jiang, and Shi-Jie Chen
Department of Physics, Department of Biochemistry, and Institute for Data Science and Informatics, University of Missouri, Columbia, Missouri.

The ability to accurately predict RNA hairpin structure and stability for different loop sequences and salt conditions is important for understanding, modeling, and designing larger RNA folds. However, traditional RNA secondary structure models cannot treat loop-sequence and ionic effects on RNA hairpin folding. Here, we describe a general, three-dimensional (3D) conformation-based computational method for modeling salt concentration-dependent conformational distributions and the detailed 3D structures for a set of three RNA hairpins that contain a variable, 15-nucleotide loop sequence. For a given RNA sequence, the new, to our knowledge, method integrates a Vfold2D two-dimensional structure folding model with IsRNA coarse-grained molecular dynamics 3D folding simulations and Monte Carlo tightly bound ion estimations of ion-mediated electrostatic interactions. The model predicts free-energy landscapes for the different RNA hairpin-forming sequences with variable salt conditions. The theoretically predicted results agree with the experimental fluorescence measurements, validating the strategy. Furthermore, the theoretical model goes beyond the experimental results by enabling in-depth 3D structural analysis, revealing energetic mechanisms for the sequence- and salt-dependent folding stability. Although the computational framework presented here is developed for RNA hairpin systems, the general method may be applied to investigate other RNA systems, such as multiway junctions or pseudoknots in mixed metal ion solutions.

UI MeSH Term Description Entries
D009690 Nucleic Acid Conformation The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape. DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D013816 Thermodynamics A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed) Thermodynamic
D056004 Molecular Dynamics Simulation A computer simulation developed to study the motion of molecules over a period of time. Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics
D059370 RNA Folding The processes of RNA tertiary structure formation. RNA Refolding,RNA Unfolding,Folding, RNA,Foldings, RNA,RNA Foldings,RNA Refoldings,RNA Unfoldings,Refolding, RNA,Refoldings, RNA,Unfolding, RNA,Unfoldings, RNA
D020871 RNA Stability The extent to which an RNA molecule retains its structural integrity and resists degradation by RNASE, and base-catalyzed HYDROLYSIS, under changing in vivo or in vitro conditions. RNA Decay,mRNA Decay,mRNA Transcript Degradation,RNA Degradation,RNA Instability,mRNA Degradation,mRNA Instability,mRNA Stability,Decay, RNA,Decay, mRNA,Degradation, RNA,Degradation, mRNA,Degradation, mRNA Transcript,Instability, RNA,Instability, mRNA,Stability, RNA,Stability, mRNA,Transcript Degradation, mRNA

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