MCTBI: a web server for predicting metal ion effects in RNA structures

Sun, Li‐Zhen; Zhang, Jingxiang; Chen, Shi‐Jie

doi:10.1261/rna.060947.117

Cited by 20 publications

(39 citation statements)

References 80 publications

(103 reference statements)

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“…We observed that dsRNA attracts more monovalent cations than dsDNA and interacts more favourably with Mg 2+ . These results indicate that the electrostatic field around the RNA duplex is stronger than that of the DNA duplex, as proposed by numerous computational studies (34)(35)(36)(37)(38)(39)65).…”

Section: Discussionsupporting

confidence: 72%

“…Yet, our knowledge of the ion atmosphere around RNA helices is limited. There are several computational studies dedicated to quantifying the RNA-ion interactions within the ion atmosphere (34)(35)(36)(37)(38)(39)(40); in particular, Poisson-Boltzmann (PB) calculations have emerged as the approach of choice, in part because it is easily implementable, computationally tractable, and conceptually straightforward (41)(42)(43)(44)(45)(46). However, there are few experimental studies on the RNA electrostatics, and the complex RNAs used typically prevents isolating and dissecting the ion atmosphere and its associated energetics (41)(42)(43)(44)(45)(46)(47)(48).…”

Section: Introductionmentioning

confidence: 99%

“…Experimental methods like ion counting can quantify the overall content of the ion atmosphere and energetics of competitive association of cations but does not provide information about the distribution of ions within the atmosphere. Computational models can in principle provide a thorough and deep understanding of ion-nucleic acid interactions, solvent-nucleic acid interactions, and the dynamic and energetic consequences of these interactions(31,35,60,(68)(69)(70)(71)(72)(73)(74)(75). However, the accuracy of such models cannot be assumed, and even matching to one a few prior experimental measurements in insufficient to establish the veracity of models for systems as complex and multi-variant as nucleic acid/ion interactions in solution.…”

mentioning

confidence: 99%

“…dsRNA we measured monovalent cation competition for binding to dsDNA and dsRNA against constant concentration of Mg 2+ . DNA and RNA preferentially interact with divalent cations [M 2+ ] over monovalent cation [M + ], and the preference for divalent over monovalent increases as the strength of the molecule's electrostatic field increases(15,35,36,39,41,64,65).Our previous ion counting measurements of Mg 2+ association with the dsDNA revealed 21.5 ± 0.5 divalent cations around the molecule for solutions containing only Mg 2+ cations(20,30). We measured the similar number of attracted Mg 2+ around 24-bp RNA, Mg 2+ ] vs. [M + ] competition experiments against two monovalent cations Na + and Cs + as competing cations [CC] to address the effect of the [CC] size (e.g.…”

mentioning

confidence: 99%

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Quantitative studies of an RNA duplex electrostatics by ion counting

Gębala

Herschlag

2019

Preprint

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Ribonucleic acids are one of the most charged polyelectrolytes in nature, and understanding of their electrostatics is fundamental to their structure and biological functions. An effective way to characterize the electrostatic field generated by nucleic acids is to quantify interactions between nucleic acids and ions that surround the molecules. These ions form a loosely associated cloud referred as an ion atmosphere. While theoretical and computational studies can describe the ion atmosphere around RNAs, benchmarks are needed to guide the development of these approaches and experiments to-date that read out RNA-ion interaction are limited. Here we present ion counting studies to quantify the number of ions surrounding well-defined model systems of 24-bp RNA and DNA duplexes. We observe that the RNA duplex attracts more cations and expels fewer anions compared to the DNA duplex and the RNA duplex interacts significantly more strongly with the divalent cation Mg 2+ . These experimental results strongly suggest that the RNA duplex generates a stronger electrostatic field than DNA, as is predicted based on the structural differences between their helices. Theoretical calculations using non-linear Poisson-Boltzmann equation give excellent agreement with experiment for monovalent ions but underestimate Mg 2+ -DNA and Mg 2+ -RNA interactions by 20%. These studies provide needed stringent benchmarks to use against other all-atom theoretical models of RNA-ion interactions, interactions that likely must be well accounted for structurally, dynamically, and energetically to confidently model RNA structure, interactions, and function.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Quantitative studies of an RNA duplex electrostatics by ion counting

Gębala

Herschlag

2019

Preprint

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“…Most recently, using a novel sampling-resampling algorithm, the Monte Carlo tightly bound ion model (MCTBI) (Sun and Chen, 2016 ) was developed in order to enhance the computational efficiency, and the partial charge-based tightly bound ion model (PCTBI) (Sun et al, 2017a ) was developed to account for more detailed RNA charge distribution. These new models have led to 1,000-fold improvement in computational time and thus allow us to treat large RNAs (several hundred nucleotides) (Sun et al, 2017c ). More importantly, these new models enable accurate predictions for RNA-RNA interactions, such the 5BSL3.2:3′X kissing interactions in HCV gRNA below, where high-resolution charge distribution can be very important.…”

Section: Computational Modeling Of Ion-rna Interactionsmentioning

confidence: 99%

Theory Meets Experiment: Metal Ion Effects in HCV Genomic RNA Kissing Complex Formation

Sun

Heng

Chen

2017

Front. Mol. Biosci.

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The long-range base pairing between the 5BSL3. 2 and 3′X domains in hepatitis C virus (HCV) genomic RNA is essential for viral replication. Experimental evidence points to the critical role of metal ions, especially Mg2+ ions, in the formation of the 5BSL3.2:3′X kissing complex. Furthermore, NMR studies suggested an important ion-dependent conformational switch in the kissing process. However, for a long time, mechanistic understanding of the ion effects for the process has been unclear. Recently, computational modeling based on the Vfold RNA folding model and the partial charge-based tightly bound ion (PCTBI) model, in combination with the NMR data, revealed novel physical insights into the role of metal ions in the 5BSL3.2-3′X system. The use of the PCTBI model, which accounts for the ion correlation and fluctuation, gives reliable predictions for the ion-dependent electrostatic free energy landscape and ion-induced population shift of the 5BSL3.2:3′X kissing complex. Furthermore, the predicted ion binding sites offer insights about how ion-RNA interactions shift the conformational equilibrium. The integrated theory-experiment study shows that Mg2+ ions may be essential for HCV viral replication. Moreover, the observed Mg2+-dependent conformational equilibrium may be an adaptive property of the HCV genomic RNA such that the equilibrium is optimized to the intracellular Mg2+ concentration in liver cells for efficient viral replication.

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Simulations of Biomolecules in Electrolyte Solutions

Friedman

2019

Advcd Theory and Sims

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Biomolecules including proteins, lipid membranes, and nucleic acids operate at an aqueous milieu that includes solvated ions. The interactions with ions affect biomolecules in different ways depending on the nature of the solute and the type of the ions. The dynamic nature of small soluble ions makes it difficult to follow them by structural methods. Consequently, theories were developed to explain how biomolecules interact in an environment that includes electrolytes. Moreover, simulations studies are often used to study such systems at the molecular or atomistic level. The status of the field, and in particular of simulation studies, is the subject of this progress report.

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MCTBI: a web server for predicting metal ion effects in RNA structures

Cited by 20 publications

References 80 publications

Quantitative studies of an RNA duplex electrostatics by ion counting

Quantitative studies of an RNA duplex electrostatics by ion counting

Theory Meets Experiment: Metal Ion Effects in HCV Genomic RNA Kissing Complex Formation

Simulations of Biomolecules in Electrolyte Solutions

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