Computational Model for Predicting Experimental RNA and DNA Nearest-Neighbor Free Energy Rankings

Johnson, Charles A.; Bloomingdale, Richard; Ponnusamy, Vikram E.; Tillinghast, Conor A.; Znosko, Brent M.; Lewis, Michael

doi:10.1021/jp2012733

Cited by 22 publications

(46 citation statements)

References 28 publications

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“…11 The cross-stacking interactions were constrained to be 12% of the total base step energies, as observed in Ref. 83. The base step energies were reduced by the average W-C base pairing energy between the two bases in the base step and their complements.…”

Section: Appendix B: Model Parametersmentioning

confidence: 99%

An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization

Hinckley

Freeman²,

Whitmer³

et al. 2013

The Journal of Chemical Physics

219

349

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A new 3-Site-Per-Nucleotide coarse-grained model for DNA is presented. The model includes anisotropic potentials between bases involved in base stacking and base pair interactions that enable the description of relevant structural properties, including the major and minor grooves. In an improvement over available coarse-grained models, the correct persistence length is recovered for both ssDNA and dsDNA, allowing for simulation of non-canonical structures such as hairpins. DNA melting temperatures, measured for duplexes and hairpins by integrating over free energy surfaces generated using metadynamics simulations, are shown to be in quantitative agreement with experiment for a variety of sequences and conditions. Hybridization rate constants, calculated using forward-flux sampling, are also shown to be in good agreement with experiment. The coarse-grained model presented here is suitable for use in biological and engineering applications, including nucleosome positioning and DNA-templated engineering. © 2013 AIP Publishing LLC.

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Section: Appendix B: Model Parametersmentioning

confidence: 99%

An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization

Hinckley

Freeman²,

Whitmer³

et al. 2013

The Journal of Chemical Physics

219

349

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show abstract

“…(Hill et al 2003). It is particularly revealing to compare the electrostatic maps of uridine and Ψ, which were generated using atomic substitution in conjunction with previously optimized geometries for U (Johnson et al 2011), operating under the assumption that Ψ assumes the same geometry as the parent U residue (Fig. 2).…”

Section: Helix To Coil Transition Of ψ-A Oligoribonucleotidesmentioning

confidence: 99%

“…Electrostatic maps for Ψ and uridine using a methyl group to simulate the electronic contribution of the ribose ring. These maps were generated in Gaussian 09 (Frisch et al 2009) using previously computed geometries for uridine (Johnson et al 2011) with the corresponding atoms being substituted to produce Ψ. this offers a convenient explanation for why 3 ′ -stacked Ψ-A parameters tend to offer additional stability to duplex formation compared to their 5 ′ -stacked counterparts. Another plausible mechanism of stabilization is that the relocated imino group is able to pull electron density away from the O4 of Ψ and thus reduce clashing with the O6 of a guanosine or O4 of a uridine in either direction.…”

Section: Helix To Coil Transition Of ψ-A Oligoribonucleotidesmentioning

confidence: 99%

Thermodynamic contribution and nearest-neighbor parameters of pseudouridine-adenosine base pairs in oligoribonucleotides

Hudson

Bloomingdale

Znosko

2013

RNA

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Pseudouridine (Ψ) is the most common noncanonical nucleotide present in naturally occurring RNA and serves a variety of roles in the cell, typically appearing where structural stability is crucial to function. Ψ residues are isomerized from native uridine residues by a class of highly conserved enzymes known as pseudouridine synthases. In order to quantify the thermodynamic impact of pseudouridylation on U-A base pairs, 24 oligoribonucleotides, 16 internal and eight terminal Ψ-A oligoribonucleotides, were thermodynamically characterized via optical melting experiments. The thermodynamic parameters derived from two-state fits were used to generate linearly independent parameters for use in secondary structure prediction algorithms using the nearestneighbor model. On average, internally pseudouridylated duplexes were 1.7 kcal/mol more stable than their U-A counterparts, and terminally pseudouridylated duplexes were 1.0 kcal/mol more stable than their U-A equivalents. Due to the fact that Ψ-A pairs maintain the same Watson-Crick hydrogen bonding capabilities as the parent U-A pair in A-form RNA, the difference in stability due to pseudouridylation was attributed to two possible sources: the novel hydrogen bonding capabilities of the newly relocated imino group as well as the novel stacking interactions afforded by the electronic configuration of the Ψ residue. The newly derived nearest-neighbor parameters for Ψ-A base pairs may be used in conjunction with other nearest-neighbor parameters for accurately predicting the most likely secondary structure of A-form RNA containing Ψ-A base pairs.

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“…Recently, Johnson et al 1 developed a method for calculating base stacking and hydrogen bonding energies for Watson-Crick pairs using average fiber diffraction geometries. 1–4 The study computationally determined energies for all standard nucleotide combinations and successfully compared these computational rankings to experimentally determined nearest neighbor (NN) free energy rankings.…”

mentioning

confidence: 99%

“…1–4 The study computationally determined energies for all standard nucleotide combinations and successfully compared these computational rankings to experimentally determined nearest neighbor (NN) free energy rankings. 1,5,6 The method resulted in rankings that agreed well with the experimental rankings, but it has not been tested on non-Watson-Crick pairs.…”

mentioning

confidence: 99%

A computational model for predicting experimental RNA nearest-neighbor free energy rankings: Inosine·uridine pairs

Jolley

Lewis

Znosko

2015

Chemical Physics Letters

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A computational model for predicting RNA nearest neighbor free energy rankings has been expanded to include the nonstandard nucleotide inosine. The model uses average fiber diffraction data and molecular dynamic simulations to generate input geometries for Quantum mechanic calculations. This resulted in calculated intrastrand stacking, interstrand stacking, and hydrogen bonding energies that were combined to give total binding energies. Total binding energies for RNA dimer duplexes containing inosine were ranked and compared to experimentally determined free energy ranks for RNA duplexes containing inosine. Statistical analysis showed significant agreement between the computationally determined ranks and the experimentally determined ranks.

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Computational Model for Predicting Experimental RNA and DNA Nearest-Neighbor Free Energy Rankings

Cited by 22 publications

References 28 publications

An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization

An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization

Thermodynamic contribution and nearest-neighbor parameters of pseudouridine-adenosine base pairs in oligoribonucleotides

A computational model for predicting experimental RNA nearest-neighbor free energy rankings: Inosine·uridine pairs

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