Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling Reveal That Different Hydrogen Bonding Patterns Are Possible for G·U Pairs:  One Hydrogen Bond for Each G·U Pair in r(GGCGUGCC)2 and Two for Each G·U Pair in r(GAGUGCUC)2,

Chen, Xiaoying; McDowell, Jeffrey A.; Kierzek, Ryszard; Krugh, Thomas R.; Turner, Douglas H.

doi:10.1021/bi992938e

Cited by 52 publications

(113 citation statements)

References 66 publications

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“…It is likely that this difference is also due to differences in Coulombic and overlap interactions because the simple hydrogen-bond model cannot rationalize this difference. Interestingly, NMR and chemical substitution effects suggest that not all adjacent G•U pairs form two hydrogen bonds (83), and molecular dynamics calculations reproduce this interpretation (84).…”

Section: Gc Ersus Cg Closure Of Tandem G•a Pairs: Versusmentioning

confidence: 95%

RNA Challenges for Computational Chemists

Yildirim

Turner

2005

Biochemistry

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Some experimental results for the thermodynamics of RNA folding cannot be explained by simple pairwise hydrogen-bonding models. Such effects include the stabilities of isoguanosineisocytidine (iG-iC) base pairs and of various 2 × 2 nucleotide internal loops. Presumably, these results can be explained by base stacking effects, which can be partitioned into Coulombic and overlap effects. We review experimental measurements that provide benchmarks for testing the approximations and theories used for modeling nucleic acids. Quantitative agreement between experiment and theory will indicate understanding of the interactions determining RNA stability and structure.An understanding of the physical-chemical interactions underlying RNA folding would allow predictions of structure and perhaps function from sequence. The large number of atoms in an RNA molecule necessitates the use of approximate methods, rather than the rigorous equations of quantum mechanics. Many approaches are possible, including coarsegrained potentials (1), which use residue-centered force fields; molecular mechanics, which uses atom-centered force fields such as AMBER (2), CHARMM (3, 4), and GROMOS (5, 6); approximate quantum mechanics, which considers interactions of electrons and nuclei (7,8); and QM/MM, which combines quantum mechanics with molecular mechanics (9-16). Depending on the property to be predicted, the size of the RNA, and the domain of interest, different approaches will provide acceptable approximations.The secondary structure of RNA can sometimes be deduced by sequence comparison, which relies on the Watson-Crick rules for base pairing and the assumption that secondary structures are more conserved than sequences for function (17). Often, however, there are not enough sequences to determine a definitive secondary structure. For these cases, freeenergy minimization with a nearest neighbor model is the most popular method for predicting secondary structures (18-38). In this method, possible secondary structure motifs are assigned free-energy parameters, and these values are added to predict the total free energy of forming a secondary structure. The structure with the lowest free energy is assumed to dominate in solution. Rigorously, however, the concentrations of the various possible structures are predicted to be weighted by a Boltzmann factor, exp(−ΔG°/RT), where ΔG° is the free energy change for folding, R is the gas constant, 1.987 cal K −1 mol −1 , and T is the temperature in kelvins. Understanding intermolecular interactions such as hydrogen bonding, stacking, and so forth would allow accurate prediction of ΔG° and therefore secondary structure for an RNA. † This work was supported by NIH Grant GM22939 (D.H.T. Watson-Crick base pairs are the most common and most extensively studied motif in RNA structures. Configurations with the same base compositions but different permutations of base pairs generally have different free energies. For example, the duplexes (5′CGCG3′) 2 and (5′GGCC3′) 2 both have four GC base pairs, bu...

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Section: Gc Ersus Cg Closure Of Tandem G•a Pairs: Versusmentioning

confidence: 95%

RNA Challenges for Computational Chemists

Yildirim

Turner

2005

Biochemistry

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“…It seems that when the p53 attempted to bend the DNA, the base pairing at the center of the half sites were perturbed and the hydrogen bonding for the AT base pairs became vulnerable to conformational changes. Previous experimental and simulation results showed that in the CATG motif, the G or A base crossstrand stacking helped maintain the stability of the duplex while in the CTAG motif such G or A base stacking is not present 36,37 . It seems that large base stacking may also help in stabilizing the bent DNA conformation upon p53 binding.…”

Section: Difference In Base Pair Parametersmentioning

confidence: 97%

p53-Induced DNA Bending: The Interplay between p53−DNA and p53−p53 Interactions

Pan

Nussinov

2008

J. Phys. Chem. B

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Specific p53 binding-induced DNA bending and its underlying driving forces are crucial for the understanding of selective transcription activation. Diverse p53-response elements exist in the genome. However, it is not known what determines the DNA bending and to what extent. In order to gain knowledge of the forces that govern the DNA bending, molecular dynamics simulations were performed on a series of p53 core domain tetramer-DNA complexes in which each p53 core domain was bound to a DNA quarter site specifically. By varying the sequence of the central 4-base pairs of each half site, different DNA bending extents were observed. Our analysis shows that the interactions between p53 dimer-dimer were similar in all complexes; on the other hand, specific interactions between the p53 and DNA, including the interactions of Arg280, Lys120 and Arg248 with the DNA varied more significantly. In particular, the Arg280 interactions were better maintained in the complex with the CATG-containing DNA sequence, and were mostly lost in the complex with the CTAG-containing DNA sequence. Structural analysis shows that the base pairings for the CATG sequence were stable throughout the simulation trajectory while those for the CTAG sequence was partially dissociated in part of the trajectory, which affected the stability of nearby Arg280-Gua base interactions. Thus, DNA bending depends on the balance between the p53 dimer-dimer interactions and p53-DNA interactions, which in turn are related to the DNA sequence and DNA flexibility.

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“…We counted two hydrogen bonds for each G:U base-pairing, following the conventional notion (Ladner et al 1975;Varani and McClain 2000), although few works indicated that the number of hydrogen bonds of G:U depend on its adjacent neighbors and can be less than two (Chen et al 2000;Vercoutere et al 2003).…”

Section: Counting the Total Number Of Hydrogen Bonds Between Two Rna mentioning

confidence: 99%

Comparative analysis detects dependencies among the 5′ splice-site positions

Carmel¹,

Tal²,

Vig³

et al. 2004

RNA

196

197

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Human-mouse comparative genomics is an informative tool to assess sequence functionality as inferred from its conservation level. We used this approach to examine dependency among different positions of the 5 splice site. We compiled a data set of 50,493 homologous human-mouse internal exons and analyzed the frequency of changes among different positions of homologous human-mouse 5 splice-site pairs. We found mutual relationships between positions +4 and +5, +5 and +6, −2 and +5, and −1 and +5. We also demonstrated the association between the exonic and the intronic positions of the 5 splice site, in which a stronger interaction of U1 snRNA and the intronic portion of the 5 splice site compensates for weak interaction of U1 snRNA and the exonic portion of the 5 splice site, and vice versa. By using an ex vivo system that mimics the effect of mutation in the 5 splice site leading to familial dysautonomia, we demonstrated that U1 snRNA base-pairing with positions +6 and −1 is the only functional requirement for mRNA splicing of this 5 splice site. Our findings indicate the importance of U1 snRNA base-pairing to the exonic portion of the 5 splice site.

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Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling Reveal That Different Hydrogen Bonding Patterns Are Possible for G·U Pairs: One Hydrogen Bond for Each G·U Pair in r(GGCGUGCC)₂ and Two for Each G·U Pair in r(GAGUGCUC)₂^,

Cited by 52 publications

References 66 publications

RNA Challenges for Computational Chemists

RNA Challenges for Computational Chemists

p53-Induced DNA Bending: The Interplay between p53−DNA and p53−p53 Interactions

Comparative analysis detects dependencies among the 5′ splice-site positions

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