期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 130, 期 37, 页码 12334-12341出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja800854u
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资金
- NIH [PO1 GM066275]
- NSF [PHY-0140140]
- U.S. Department of Energy [DE-AC03-76SF00098]
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
Electrostatic forces, acting between helices and modulated by the presence of the ion atmosphere, are key determinants in the energetic balance that governs RNA folding. Previous studies have employed Poisson-Boltzmann (PB) theory to compute the energetic contribution of these forces in RNA folding. However, the complex interaction of these electrostatic forces with RNA features such as tertiary contact formation, specific ion-binding, and complex interhelical junctions present in prior studies precluded a rigorous evaluation of PB theory, especially in physiologically important Mg2+ solutions. To critically assess PB theory, we developed a model system that isolates these electrostatic forces. The model system, composed of two DNA duplexes tethered by a polyethylene glycol junction, is an analog for the unfolded state of canonical helix-junction-helix motifs found in virtually all structured RNAs. This model system lacks the complicating features that have precluded a critical assessment of PB in prior studies, ensuring that interhelical electrostatic forces dominate the behavior of the system. The system's simplicity allows PB predictions to be directly compared with small-angle X-ray scattering experiments over a range of monovalent and divalent ion concentrations. These comparisons indicate that PB is a reasonable description of the underlying electrostatic energies for monovalent ions, but large deviations are observed for divalent ions. The validation of PB for monovalent solutions allows analysis of the change in the conformational ensemble of this simple motif as salt concentration is changed. Addition of ions allows the motif to sample more compact microstates, increasing its conformational entropy. The increase of conformational entropy presents an additional barrier to folding by stabilizing the unfolded state. Neglecting this effect will adversely impact the accuracy of folding analyses and models.
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