yDNA versus xDNA Pyrimidine Nucleobases: Computational Evidence for Dependence of Duplex Stability on Spacer Location

Lait, Linda A.; Rutledge, Lesley R.; Millen, Andrea L.; Wetmore, Stacey D.

doi:10.1021/jp805547p

Cited by 19 publications

(44 citation statements)

References 84 publications

(277 reference statements)

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“…As a step towards testing this hypothesis, we analyze the inherent stacking potential of CA and TAP. Previous computational studies have characterized the stacking interactions in dimers composed of nucleobases and/or other heterocycles . Despite the dependence of these interactions on translational (i. e. vertical and horizontal monomer displacements) and rotational (i. e., mutual rotation of the interacting monomers) geometric variables, these studies reveal the stacking strength most prominently depends on the rotational parameter .…”

Section: Resultsmentioning

confidence: 99%

“…Previous computational studies have characterized the stacking interactions in dimers composed of nucleobases and/or other heterocycles . Despite the dependence of these interactions on translational (i. e. vertical and horizontal monomer displacements) and rotational (i. e., mutual rotation of the interacting monomers) geometric variables, these studies reveal the stacking strength most prominently depends on the rotational parameter . Thus, in the present work, we consider the dependence of the strength of the stacking interactions on the angle of rotation ( α ) between monomers aligned with respect to their ring centers at a fixed vertical distance (3.3 Å), which is the average separation between bases in nucleic acid helices, and was chosen to parallel studies on nucleobase dimers …”

Section: Resultsmentioning

confidence: 99%

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Can Cyanuric Acid and 2,4,6‐Triaminopyrimidine Containing Ribonucleosides be Components of Prebiotic RNA? Insights from QM Calculations and MD Simulations

2019

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As a step toward assessing their fitness as pre‐RNA nucleobases, we employ DFT and MD simulations to analyze the noncovalent interactions of cyanuric acid (CA) and 2,4,6‐triaminopyrimidine (TAP), and the structural properties of the associated ribonucleosides (rNs) and oligonucleotides. Our calculations reveal that the TAP : CA pair has a comparable hydrogen‐bond strength to the canonical A : U pair. This strengthens the candidature of CA and TAP as prebiotic nucleobases. Further, the stacking between two canonical nucleobases is stronger than those between TAP or CA and a canonical base, as well as those between two TAP and/or CA, which indicates that enhanced stacking may have served as a driving force for the evolution from prebiotic to canonical nucleobases. Similarities in the DFT‐derived anti/syn rotational barriers and MD‐derived (anti) glycosidic conformation of the CA and TAP rNs and canonical rNs further substantiate their candidature as pre‐RNA components. Greater deglycosylation barriers (as obtained by DFT calculations) for TAP rNs compared to canonical rNs suggest TAP rNs indicate higher resistance to environmental factors, while lower barriers indicate that CA rNs were likely more suitable for less‐challenging locations. Finally, the tight packing in narrow CA:TAP‐containing helices suggests that the prebiotic polymers were shielded from water, which would aid their evolution into self‐replicating systems. Our calculations thus support proposals that CA and TAP can act as nucleobases of pre‐RNA.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Can Cyanuric Acid and 2,4,6‐Triaminopyrimidine Containing Ribonucleosides be Components of Prebiotic RNA? Insights from QM Calculations and MD Simulations

2019

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“…Quantum chemical calculations estimate that interactions in a double helix composed of xDNA are 10-15% stronger in expanded DNA compared to typical interactions native DNA [30]. The origin of the effect is not hydrogen bond strength, which should be nearly identical in xDNA and yDNA compared to native DNA [31]. Rather the base stacking interactions are the origin of the increased stability, which is manifest in the change in melting temperature from [27].…”

Section: Expanded Dna and Modification Of The Base Stackmentioning

confidence: 98%

Thermodynamics of Nucleic Acid Structural Modifications for Biotechnology Applications

Franzen¹

2011

Biotechnology of Biopolymers

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IntroductionThe repertoire of chemistry available to native nucleotides in DNA and RNA is limited to the purine and pyrimidine functional groups, along with the special role of the 2'-hydroxyl of RNA. The nucleobases have exocyclic amino groups and imines, neither of which is highly reactive or a good candidate for catalytic function. One might argue that the limited range of chemical reactivity is an evolutionary advantage in molecules whose functions are primarily to store (DNA) and process (RNA) genetic information. The most important attribute of both DNA and RNA is the molecular recognition through base pairing. The hydrogen bond pattern combined with the conformation of the ribose sugar gives rise to the specific B-form double helix in DNA and A-form helix with a range of additional standard folds in RNA, loops, bulges and pseudoknots. These structures are well known for their ability to interact with proteins to provide a scaffold for transcription (DNA → RNA) to create messenger RNA (mRNA), and processing of mRNA by enzymes that have active components composed of RNA molecules. The chemical action of RNA on other RNAs by means of the 2'-hydroxyl is an exception to the lack or reactivity of DNA and RNA. Selfsplicing by action of the 2'-hydroxyl as a nucleophile was the process that broke the dogma that RNA is always a passive molecule that simply transmits information [1]. Indeed, RNA i s v e r y a c t i v e i n p r o c e s s i n g o t h e r R N A s u s i n g t h e 2 ' -h y d r o x y l a s a n u c l e o p h i l e f o r hydrolysis of the phosphodiester bond leading to cleavage or to rearrangements of structure such as RNA splicing. Outside of this reactivity, the components of the purine and pyrimidine rings are largely inert. Aromatic amines are poor nucleophiles, and imines are even less reactive. The purine and pyrimidine rings are not particularly electrophilic because of the nitrogen heteroatoms and carbonyls. Using in vitro selection (also known as SELEX) [2][3][4], and appropriate modification, RNA and DNA have been developed for numerous applications that transcend their biological functions. In this chapter we will consider the modifications of the nucleobase as a means to expand upon the native function. The extensive literature on modifications of the phosphodiester backbone and the ribose sugar will not be considered in this chapter due to space limitations. Base modifications may consist of expansions of the purine/pyrimidine ring, appended functional group or chemical modification to increase the stability of the backbone with respect to hydrolysis. Expanded DNA or xDNA has been developed as mimics of native DNA with potential biotechnology applications [5,6]. In these molecules, the purine and pyrimidine rings are fused to phenyl or naphthyl rings to give rise to

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“…Increased base surface area of size expanded yDNA helices make them more thermally stable than their natural counterparts with a greater stacking affinity due to hydrophobicity . The fluorescent properties exhibited by xDNA and yDNA oligomers suggest their possible use in detection or imaging of natural nucleic acid sequences.…”

Section: Introductionmentioning

confidence: 99%

“…Size expanded nucleobases can also be used to probe steric effects in the active sites of polymerase enzymes . Compared to natural DNA, xDNA and yDNA bases pairs have potentially enhanced charge transfer properties due to their larger conjugated π systems . Both xDNA and yDNA have a high melting point and smaller HOMO‐LUMO gaps than the natural DNA which makes them function as nanowires …”

Section: Introductionmentioning

confidence: 99%

Conformational features of benzo‐homologated yDNA duplexes by molecular dynamics simulation

et al. 2015

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yDNA is a base-modified nucleic acid duplex containing size-expanded nucleobases. Base-modified nucleic acids could expand the genetic alphabet and thereby enhance the functional potential of DNA. Unrestrained 100 ns MD simulations were performed in explicit solvent on the yDNA NMR sequence [5'(yA T yA yA T yA T T yA T) ] and two modeled yDNA duplexes, [5'(yC yC G yC yC G G yC G G) ] and [(yT5' G yT A yC yG C yA yG T3')•(yA5' C T C yG C G yT A yC A3')]. The force field parameters for the yDNA bases were derived in consistent with the well-established AMBER force field. Our results show that DNA backbone can withstand the stretched size of the bases retaining the Watson-Crick base pairing in the duplexes. The duplexes retained their double helical structure throughout the simulations accommodating the strain due to expanded bases in the backbone torsion angles, sugar pucker and helical parameters. The effect of the benzo-expansion is clearly reflected in the extended C1'-C1' distances and enlarged groove widths. The size expanded base modification leads to reduction in base pair twist resulting in larger overlapping area between the stacked bases, enhancing inter and intra strand stacking interactions in yDNA in comparison with BDNA. This geometry could favour enhanced interactions with the groove binders and DNA binding proteins., 2016. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 55-64, 2016.

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yDNA versus xDNA Pyrimidine Nucleobases: Computational Evidence for Dependence of Duplex Stability on Spacer Location

Cited by 19 publications

References 84 publications

Can Cyanuric Acid and 2,4,6‐Triaminopyrimidine Containing Ribonucleosides be Components of Prebiotic RNA? Insights from QM Calculations and MD Simulations

Can Cyanuric Acid and 2,4,6‐Triaminopyrimidine Containing Ribonucleosides be Components of Prebiotic RNA? Insights from QM Calculations and MD Simulations

Thermodynamics of Nucleic Acid Structural Modifications for Biotechnology Applications

Conformational features of benzo‐homologated yDNA duplexes by molecular dynamics simulation

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