Ion distributions around left- and right-handed DNA and RNA duplexes: a comparative study

Pan, Feng; Roland, Christopher; Sagui, Celeste

doi:10.1093/nar/gku1107

Cited by 53 publications

(66 citation statements)

References 123 publications

(130 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 71%

“…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%

See 1 more Smart Citation

Quantitative studies of an RNA duplex electrostatics by ion counting

Gębala

Herschlag

2019

Preprint

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Quantitative studies of an RNA duplex electrostatics by ion counting

Gębala

Herschlag

2019

Preprint

View full text Add to dashboard Cite

show abstract

“…A Na + ion can stabilize a G-G mismatch by forming an ion bridge connecting the G(O6) atoms in the four G bases in a double G-G mismatch (Figure 12a); or the two bases in a single G-G mismatch and the two bases in the adjacent G-C base pair (Figure 12b). These pockets are very similar to the Na + ion trapped in a (CG) 6 duplex, where the ion is held by two G(O6) and two C(N4), in both B-DNA and A-RNA (see Figure 14a and b in ref 22). …”

Section: Resultsmentioning

confidence: 67%

“…Figures S11 and S12 show the neutralizing Na + ion occupation as a function of base pairs in the major and minor grooves, and Figure 12 shows some typical patterns for ions involved in direct binding to the mismatched bases. We know from studies of ion distributions in the sequence (CG) 6 22 that neutralizing Na + ions sit preferentially around the G bases in the major grooves, both in B-DNA and A-RNA forms. This trend is clearly seen in the G-rich duplexes in Figures S11 and S12 where the amount of ions in the minor groove is completely negligible and most of them sit in the major groove, especially around the G-G mismatches.…”

Section: Resultsmentioning

confidence: 99%

Structure and Dynamics of DNA and RNA Double Helices Obtained from the GGGGCC and CCCCGG Hexanucleotide Repeats That Are the Hallmark of C9FTD/ALS Diseases

Zhang

Roland

Sagui

2016

ACS Chem. Neurosci.

Self Cite

View full text Add to dashboard Cite

A (GGGGCC) hexanucleotide repeat (HR) expansion in the C9ORF72 gene, and its associated antisense (CCCCGG) expansion, are considered the major cause behind frontotemporal dementia and amyotrophic lateral sclerosis. We have performed molecular dynamics simulations to characterize the conformation and dynamics of the 12 duplexes that result from the three different reading frames in sense and antisense HRs for both DNA and RNA. These duplexes display atypical structures relevant not only for a molecular level understanding of these diseases but also for enlarging the repertoire of nucleic-acid structural motifs. G-rich helices share common features. The inner G-G mismatches stay inside the helix in Gsyn-Ganti conformations and form two hydrogen bonds (HBs) between the Watson–Crick edge of Ganti and the Hoogsteen edge of Gsyn. In addition, Gsyn in RNA forms a base-phosphate HB. Inner G-G mismatches cause local unwinding of the helix. G-rich double helices are more stable than C-rich helices due to better stacking and HBs of G-G mismatches. C-rich helix conformations vary wildly. C mismatches flip out of the helix in DNA but not in RNA. Least (most) stable C-rich RNA and DNA helices have single (double) mismatches separated by two (four) Watson–Crick basepairs. The most stable DNA structure displays an “e-motif” where mismatched bases flip toward the minor groove and point in the 5′ direction. There are two RNA conformations, where the orientation and HB pattern of the mismatches is coupled to bending of the helix.

show abstract

“…27−33 These simulations typically reveal cations in helical grooves, with a size dependence to this occupancy, 29,31,32,34−39 and greater accumulation of smaller cations around phosphoryl oxygen atoms. 30,31,37,40,41 Thus, computational approaches have provided general support for cation size as an important determinant of cation position in and occupancy of the ion atmosphere and of the ion atmosphere’s ability to screen nucleic acid charge.…”

Section: Introductionmentioning

confidence: 99%

Does Cation Size Affect Occupancy and Electrostatic Screening of the Nucleic Acid Ion Atmosphere?

et al. 2016

View full text Add to dashboard Cite

Electrostatics are central to all aspects of nucleic acid behavior, including their folding, condensation, and binding to other molecules, and the energetics of these processes are profoundly influenced by the ion atmosphere that surrounds nucleic acids. Given the highly complex and dynamic nature of the ion atmosphere, understanding its properties and effects will require synergy between computational modeling and experiment. Prior computational models and experiments suggest that cation occupancy in the ion atmosphere depends on the size of the cation. However, the computational models have not been independently tested, and the experimentally observed effects were small. Here, we evaluate a computational model of ion size effects by experimentally testing a blind prediction made from that model, and we present additional experimental results that extend our understanding of the ion atmosphere. Giambasu et al. developed and implemented a three-dimensional reference interaction site (3D-RISM) model for monovalent cations surrounding DNA and RNA helices, and this model predicts that Na+ would outcompete Cs+ by 1.8–2.1-fold; i.e., with Cs+ in 2-fold excess of Na+ the ion atmosphere would contain an equal number of each cation (Nucleic Acids Res.2015, 43, 8405). However, our ion counting experiments indicate that there is no significant preference for Na+ over Cs+. There is an ∼25% preferential occupancy of Li+ over larger cations in the ion atmosphere but, counter to general expectations from existing models, no size dependence for the other alkali metal ions. Further, we followed the folding of the P4–P6 RNA and showed that differences in folding with different alkali metal ions observed at high concentration arise from cation–anion interactions and not cation size effects. Overall, our results provide a critical test of a computational prediction, fundamental information about ion atmosphere properties, and parameters that will aid in the development of next-generation nucleic acid computational models.

show abstract

Ion distributions around left- and right-handed DNA and RNA duplexes: a comparative study

Cited by 53 publications

References 123 publications

Quantitative studies of an RNA duplex electrostatics by ion counting

Quantitative studies of an RNA duplex electrostatics by ion counting

Structure and Dynamics of DNA and RNA Double Helices Obtained from the GGGGCC and CCCCGG Hexanucleotide Repeats That Are the Hallmark of C9FTD/ALS Diseases

Does Cation Size Affect Occupancy and Electrostatic Screening of the Nucleic Acid Ion Atmosphere?

Contact Info

Product

Resources

About