Nucleic Acid Conformation Research Articles

Electric dichroism and birefringence for determining the conformation of nucleic acids in solution.

Electric dichroism and birefringence for determining the conformation of nucleic acids in solution.

Solvent interactions stabilising nucleic acid conformers.

The transition of oligonucleotides from the B to the A conformation has been studied by the use of simple geometric calculations aimed at finding possible hydration sites which could stabilize these conformations. The method involves the classification of equally spaced grid points, surrounding the oligonucleotide, into groups depending on whether a water molecule, so placed, could form single, multiple or nil contacts to polar oligonucleotide atoms. The occurrence of the multiple, and therefore bridging, sites is more extensive for the 'A' than the 'B' conformation. Thus, more general evidence is presented in support of the economy of hydration hypothesis in which phosphate groups, in the low humidity 'A' form, have been seen to be bridged by single water molecules. Similar calculations for the 'Z' DNA conformation show a different preference for multiple bridging sites.

Application of two‐dimensional NMR spectroscopy in the determination of solution conformation of nucleic acids

AbstractTwo‐dimensional NMR has developed into an important tool for the study of solution structures of nucleic acids. The conformational information is generally derived from the three bond coupling constants (J) and interproton distances (r). Strategies have been developed to obtain J values using COSY and J‐resolved spectroscopy. Estimation of interproton distances involves measurement of NOESY build‐up curves as a function of mixing time. This information can be coupled with structural refinement techniques to obtain the three‐dimensional structure of nucleic acids. Here we have described the current status of this important field with particular reference to advancements in applications to DNA structures.

Ab initio molecular orbital study on the pairing and stacking interactions between nucleic acid bases in relation to the biological activities

Ab initio molecular orbital calculations were performed on the pairing and stacking interaction energies between bases in nucleic acids. Using these values we could explain the biologically important phenomena well. Thus the fact that O 6-methylguanine (which is formed in small amounts) is more promutagenic than N 7-methylguanine (which is formed in larger amounts) could be explained by the difference in pairing interaction energies for these alkylguanines. To clarify the detailed mechanism of mutation induced by a base analogue (2-aminopurine) the interaction energy for the 2-aminopurine-cytosine pair was calculated by taking into account the tautomeric conversion of base and the base analogue. It was concluded that the base pair formed as an intermediate between the normal form of 2-aminopurine and the imino tautomer of cytosine has an important role in inducing the mutation by 2-aminopurine. The stacking interaction energy was found to be a principal factor in determining the conformation of nucleic acids, and it predicted the preference for the A-form or B-form of the deoxyoligonucleotides well. The stacking interaction energy was resolved into its components, and it was shown that electrostatic energy was base sequence-dependent, whereas the overall stability of the stacked polymers was largely dependent on the dispersion energy.

FUS: a system to simulate conformational changes in biological macromolecules.

In order to study the dynamics of protein and nucleic acid conformations, a molecular folding-unfolding system (FUS written in Lisp) has been developed. Secondary structure features of protein and nucleic acids are graphically represented by cubes in a modified 'Blocks World' paradigm. Modeling of protein and nucleic acid unfolding (denaturation) and folding of their three-dimensional structure is possible by the use of high level 'block' operators which allow displacement of these structural features in space. Due to the flexible nature of this program, FUS is a useful tool for the rapid evaluation of user-defined rules governing conformational changes. The use of FUS to unfold three common proteins (prealbumin, flavodoxin and triose phosphate isomerase) and a tRNA is presented.

Energetics of left-handed helix formation of nucleic acids

The inversion of canonical right-handed double helical conformations of nucleic acids (B-DNA, A-RNA) into the left-handed form, due to changes in the polymer environment, can be followed by a variety of physical methods such as UV-, CD-, or NMR-spectroscopy. The only quantitative approach to the evaluation of the energy parameters in based on adiabatic scanning microcalorimetry. The results presented in this paper demonstrate that the inversion process is accompanied by an enthalpy change of about 5 KJ per mole basepairs and an entropy change of about 14 J per degree and mole basepairs. The inversion temperature for the thermally induced transition is about 45°C in almost all cases. This holds both for DNA- as well as RNA-sequences.

Ultraviolet resonance Raman bands of guanosine and adenosine residues useful for the determination of nucleic acid conformation

AbstractThe ultraviolet resonance Raman (UVRR) bands of several guanine‐ and adenine‐containing mononucleotides were measured, and were compared with the classical and UVRR spectra of 9‐ethylguanine, which contains no furanose ring, in order to assess the effect of sugar conformation on the UVRR spectrum. For several guanine mononucleotides containing different furanose rings some differences were found in the Raman bands normally attributed to the purine vibrations. A similar effect exists with different adenosine mononucleotides. The fact that these vibrations are allowed in the rigorous resonance Raman effect indicates that they are coupled to the electronic transitions of the base. Differences which are seen between cyclic nucleotides, ribonucleotides and deoxyribonucleotides probably arise from differences in the conformation of the attached furanose rings. This provides a method for the identification of conformationally sensitive vibrations of purine rings in nucleic acids.

Hydration of Nucleic Acid Crystalsa

Can we make any generalizations from examination of the crystal structures in hand? The results of study of the very well-determined high-resolution structures indicate that the counterions have a very strong effect on organizing the water structure and that these counterions are bonded in a sequence-specific manner. Hence, the sodium ion bonds in the minor groove of ApU and only to the phosphate backbone in GpC. Not surprisingly then, the water network in ApU is predominantly in its minor groove. Similarly, the negative sulfate counterion in the major groove of the 3:2 complex between proflavine and CpG has a significant influence on the water structure in that crystal. The crystallization of two positive proflavine molecules with two negative nucleic acid chains obviates the need for inorganic ions and may provide additional insight about nucleic acid water structure. The presence of the charged aromatic hydrocarbon appears to provide the correct mixture of hydrophilicity and hydrophobicity that allows for both the gathering and ordering of water molecules around the nucleic acid molecule, not unlike what was previously observed in the semiclathrate structures. This same type of hydrophobic aggregation might pertain along the major groove side of structures containing the appropriate arrangement of methyl-containing thymine bases. Although it is very tempting at this point to make further rules and predictions, experience has shown that, especially in the case of nucleic acids, such prognostications would be premature. What is clearly needed are some more high-quality crystal structures of a variety of sequences under different and controlled conditions. Analyses of these may then put us in a position to successfully predict both the structure of water and its effects on nucleic acid conformation.

Vacuum ultraviolet circular dichroism of double stranded nucleic acids.

AbstractThe vacuum ultraviolet (VUV) circular dichroism (CD) of double stranded DNA and RNA is greater in amplitude than the CD of these molecules for wavelengths longer than 200 nm. The amplitude of the VUV‐CD depends on the base composition of DNA, with guanine‐cytosine base pairs contributing more intensity than adenine‐thymine base pairs. The shape and amplitude of the VUV‐CO are better indicators of nucleic acid conformation (A, B or Z) than are those of the longer wavelength CD. We illustrate the unique features of VUV‐CD with specific examples. In the presence of Cs+ and ethanol, VUV‐CD reveals that poly(dA‐dC)poly(dG‐dT) forms a right handed double helix despite the inversion of the longer wavelength CD, which usually is used as a benchmark for the left‐handed form. The greater magnitude of the VUV‐CD of DNA and RNA compared to longer wavelengths means that the VUV‐CD is less susceptible to distortion by the induced CD of UV‐absorbing ligands like mitomycin C and N‐2‐acetylaminofluorene.

A theoretical investigation of the sequence specificity in the binding of the antitumor drug anthramycin to DNA.

A theoretical study is presented concerning DNA-anthramycin adducts. By explicit energy minimisations using a semi-empirical energy formula and an advanced algorithm the structural properties and the energetics of this system are analysed. The results obtained demonstrate that the formation of a covalently bound adduct in which anthramycin is attached to the N2 site of a guanine within a DNA fragment is accompanied by a considerable change in the nucleic acid conformation as confirmed by recent experimental evidence. With the use of the "SIR" methodology for treating DNA flexibility the general features of this change are characterised. The sequence specificity of anthramycin binding is investigated and the important role of sequence dependent nucleic acid flexibility brought to light. This theoretical treatment thus provides new elements for the interpretation of the origins of ligand binding specificities.

The significance of the aprotic solvent in monomer studies related to the primary subunit environment in the macromolecule

An advantage of aprotic polar solvent systems in the study of monomer interactions relevant to the macromolecular state is demonstrated with the measurement of nucleoside amino proton exchange rates in DMSO/water mixtures. The DMSO/water solvent provides the first unequivocal observation of general acid catalysis of nucleic acid amino proton exchange, which is undetectable in aqueous solution due to the formation of the endocyclic protonated nucleobase. Suppression of nucleobase protonation in the presence of buffer acid is a consequence of anion desolvation in the aprotic solvent. The detected route of general acid catalysis is demonstrated as a consequence of Watson-Crick H-bonding, leading to the implication that amino chemistry is modulated in the helical state to decrease amino proton lifetime in the “closed” macromolecular context of conformational information obtained by hydrogen exchange methods. This useful property of the aprotic solvent can be extended to monomeric studies pertaining to specific local site interactions affecting the function and conformation of proteins and nucleic acids.

On loopfolding in nucleic acid hairpin-type structures29

In a series of studies, combining NMR, optical melting and T-jump experiments, it was found that DNA hairpins display a maximum stability when the loop part of the molecule comprises four or five nucleotide residues. This is in contrast with the current notion based on RNA hairpin studies, from which it had been established that a maximum hairpin stability is obtained for six or seven residues in the loop. Here we present a structural model to rationalize these observations. This model is based on the notion that to a major extent base stacking interactions determine the stability of nucleic acid conformations. The model predicts that loop folding in RNA is characterized by an extension of the base stacking at the 5'-side of the double helix by five or six bases; the remaining gap can then easily be closed by two nucleotides. Conversely, loop folding in DNA is characterized by extending base stacking at the 3'-side of the double helical stem by two or three residues; again bridging of the remaining gap can then be achieved by one or two nucleotides. As an example of loop folding in RNA the anticodon loop of yeast tRNAPhe is discussed. For the DNA hairpin formed by d(ATCCTAT4TAGGAT) it is shown that the loop structure obtained from molecular mechanics calculations obeys the above worded loop folding principles.

Transition from B to Z DNA: contribution of internal fluctuations to the configurational entropy difference.

The internal motions of the double-stranded DNA oligomer (dCdG)3 (dC, deoxycytidylate; dG, deoxyguanylate) in the B and Z forms have been calculated in the harmonic approximation. A complete vibrational analysis has been made, and the resulting normal mode frequencies have been used to evaluate the vibrational entropy of B and Z DNA. The greater flexibility of the B DNA hexamer leads to an entropic stabilization relative to the stiffer Z DNA hexamer of 22 calories per mole per kelvin at 300 K. The calculated value is of the same order as that (21 to 27 calories per mole per kelvin) obtained from nuclear magnetic resonance measurements on the methylated duplexes (m5dCdG)3 and (dCdGm5dCdGdCdG). This result demonstrates the importance of internal motions, which have been neglected in earlier studies of the transition from B to Z DNA, in the stability of different nucleic acid conformers.

Comparison of interproton distances in DNA models with nuclear Overhauser enhancement data

The conformational flexibility inherent in the polynucleotide chain plays an important role in deciding its three-dimensonal structure and enables it to undergo structural transitions in order to fulfil all its functions. Following certain stereochemical guidelines, both right and left handed double-helical models have been built in our laboratory and they are in reasonably good agreement with the fibre patterns for various polymorphous forms of DNA. Recently, nuclear magnetic resonance spectroscopy has become an important technique for studying the solution conformation and polymorphism of nucleic acids. Several workers have used 1H nuclear magnetic resonance nuclear Overhauser enhancement measurements to estimate the interproton distances for the various DNA oligomers and compared them with the interproton distances for particular models of A and Β form DNA. In some cases the solution conformation does not seem to fit either of these models. We have been studying various models for DNA with a view to exploring the full conformational space allowed for nucleic acid polymers. In this paper, the interproton distances calculated for the different stereochemically feasible models of DNA are presented and they are compared and correlated against those obtained from 1Η nuclear magnetic resonance nuclear Overhauser enhancement measurements of various nucleic acid oligomers.

Evidence for Z-form RNA by vacuum UV circular dichroism

Circular dichroism (CD) spectra in the vacuum UV region for different conformations of poly d(G-C) X poly d(G-C) and poly r(G-C) X poly r(G-C) are very characteristic. The CD of the RNA in the A-form (6 M NaClO4 and 22 degrees C) is very similar to that of the DNA in 80% alcohol where it is believed to be in the A-form. With the exception of the longest wavelength transition, the CD of the RNA in 6 M NaClO4 at 46 degrees C is similar to the CD of the DNA under conditions where it is believed to be in the Z-form (2 M NaClO4). This substantiates that poly r(G-C) X poly r(G-C) assumes a left-handed Z-conformation in 6 M NaClO4 above 35 degrees C. CD spectra for the left-handed Z-forms of both the RNA and DNA are characterized by an intense negative peak at 190-195 nm, a crossover at about 184 nm, and an intense positive peak below 180 nm. The right-handed A- and B-forms of RNA and DNA all have an intense positive peak in their CD spectra near 186 nm. The large difference in CD in the range 185-195 nm for right- and left-handed conformations of nucleic acids can be used to identify the sense of helix winding.

The DNA phosphate orientation. Infrared data and energetically favorable structures.

AbstractThe conformation of nucleic acids can be probed reliably by the geometrical arrangement of the PO2‐ groups in the backbone. The phosphate arrangement is described by two angles, θOO and θOPO, which can be determined by several methods. In the present paper, the two angles obtained for the A, B, and C forms of DNA, experimentally by ir linear dichroism (LD) of oriented films as well as theoretically from energy‐minimized structures. The methodology of the phosphate angle determination from the ir dichroism spectra is presented in detail, elucidating the potentialities and limitations of this method. Advantageously, tilt and twist angles of the DNA bases, found by theoretical calculations, were used in the ir data processing. The phosphate angles were compared with the corresponding x‐ray and nmr results from the literature. Regarding the rather high flexibility of the double helix, as well as the sequence‐dependent variation of the conformational angles, a fairly good agreement between our results and the majority of all discussed data can be established. Thus ir LD provides reliable data on the orientation of phosphate groups in DNA. Reasons for discrepancies with some literature data from x‐ray fiber‐diffraction analysis, published several years ago, will be discussed.

Polyamines bound to nucleic acids during dormancy and activation of tuber cells of Helianthus tuberosus

Tuber tissue of Helianthus tuberosus L. (cv. OB1) contains a low amount of polyamines during dormancy but they are rapidly synthesized when tuber cells are activated in a growth medium and enter a new cell cycle. It was assumed that one of the reasons for this synthesis is that polyamines are necessary for the active conformation and correct functioning of nucleic acids. Complexes were found between spermine, spermidine and putrescine and rRNA, tRNA and an RNA fraction which contains poly(A) RNA and proteins. The amount of RNA‐bound polyamines in the parenchyma cells of dormant tubers is dependent on the stage of dormancy and clearly increases (especially putrescine) when cells are activated. There are both tightly‐bound and non‐tightlybound polyamines. The significance of these bound polyamines is discussed in relation to their stabilizing role on nucleic acids.

Structural and sequence-dependent aspects of drug intercalation into nucleic acids.

Information gained from X-ray crystallographic studies on drug-nucleic acid complexes is described, with emphasis on the intercalation process. Relevant data from NMR experiments are examined in order to highlight similarities and differences between solution and solid-state structures. Theoretical analyses of intercalation complexes are also discussed and evaluated, with respect to the structural methods, with special reference being made to nucleic acid conformation and positions of drug molecules in the binding sites.

ChemInform Abstract: FLUCTUATIONS IN NUCLEIC ACID CONFORMATIONS. 2. RAMAN SPECTROSCOPIC EVIDENCE OF VARYING RING PUCKER IN A‐T POLYNUCLEOTIDES

Chemischer InformationsdienstVolume 14, Issue 22 Physical Organic Chemistry ChemInform Abstract: FLUCTUATIONS IN NUCLEIC ACID CONFORMATIONS. 2. RAMAN SPECTROSCOPIC EVIDENCE OF VARYING RING PUCKER IN A-T POLYNUCLEOTIDES G. A. THOMAS, G. A. THOMASSearch for more papers by this authorW. L. PETICOLAS, W. L. PETICOLASSearch for more papers by this author G. A. THOMAS, G. A. THOMASSearch for more papers by this authorW. L. PETICOLAS, W. L. PETICOLASSearch for more papers by this author First published: May 31, 1983 https://doi.org/10.1002/chin.198322049AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume14, Issue22May 31, 1983 RelatedInformation

Fluctuations in nucleic acid conformations. 2. Raman spectroscopic evidence of varying ring pucker in A-T polynucleotides

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluctuations in nucleic acid conformations. 2. Raman spectroscopic evidence of varying ring pucker in A-T polynucleotidesGerald A. Thomas and Warner L. PeticolasCite this: J. Am. Chem. Soc. 1983, 105, 4, 993–996Publication Date (Print):February 1, 1983Publication History Published online1 May 2002Published inissue 1 February 1983https://doi.org/10.1021/ja00342a058RIGHTS & PERMISSIONSArticle Views83Altmetric-Citations100LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (471 KB) Get e-Alerts Get e-Alerts