PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Nucleic Acid Conformation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2005

Cyclohexenyl nucleic acids: conformationally flexible oligonucleotides.

Cyclohexenyl nucleic acid (CeNA) is a nucleic acid mimic, where the (deoxy)ribose sugar has been replaced by cyclohexenyl moieties. In order to study the conformation of cyclohexenyl nucleosides by NMR, the HexRot program was developed to calculate conformations from scalar coupling constants of cyclohexenyl compounds, analogous to the methods applied for (deoxy)ribose nucleosides. The conformational equilibria and the values of the thermodynamic parameters are very similar between a cyclohexenyl nucleoside [energy difference between 2H3 (N-type) and 2H3 (S-type) is 1.8 kJ/mol and equilibrium occurs via the eastern hemisphere with a barrier of 10.9 kJ/mol] and a natural ribose nucleoside (energy difference between N-type and S-type is 2 kJ/mol and equilibrium occurs via the eastern hemisphere with a barrier of 4-20 kJ/mol). The flexibility of the cyclohexenyl nucleoside was demonstrated by the fast equilibrium between two conformational states that was observed in a CeNA-U monomer, combined with the 2H3 conformation of the cyclohexene moiety when incorporated into a Dickerson dodecamer and the 2H3 conformation when incorporated in a d(5'-GCGT*GCG-3')/d(5'-CGCACGC-3') duplex, as determined by the NMR spectroscopy. This represents the first example of a synthetic nucleoside that adopts different conformations when incorporated in different double-stranded DNA sequences.

Base Sequence↗
PubMed1996

Calculations of nucleic acid conformations.

The present computational power and sophistication of theoretical approaches to nucleic acid structural investigation are sufficient for the realization of static and dynamic models that correlate accurately with current crystallographic, NMR and solution-probing structural data, and consequently are able to provide valuable insights and predictions for a variety of nucleic acid conformational families. In molecular dynamics simulations, the year 1995 was marked by the foray of fast Ewald methods, an accomplishment resulting from several years' work in the search for an adequate treatment of the electrostatic long-range forces so primordial in nucleic acid behavior. In very large systems, and particularly in the RNA-folding field, techniques originating from artificial intelligence research, like constraint satisfaction programming or genetic algorithms, have established their utility and potential.

DNA↗
PubMed1999

Consequences of nucleic acid conformation on the binding of a trinuclear platinum drug.

BBR3464, a charged trinuclear platinum compound, is the first representative of a new class of anticancer drugs to enter phase I clinical trials. The structure of BBR3464 is characterized by two [trans-PtCl(NH(3))(2)] units linked by a tetraamine [trans-Pt(NH(3))(2)¿H(2)N(CH(2))(6)NH(2)¿(2)] unit. The +4 charge of BBR3464 and the separation of the platinating units indicate that the mode of DNA binding will be distinctly different from those of classical mononuclear drugs such as cisplatin, cis-[PtCl(2)(NH(3))(2)]. The reaction of BBR3464 with three different nucleic acid conformations was assessed by gel electrophoresis. Comparison of single-stranded DNA, RNA, and double-stranded DNA indicated that the reaction of BBR3464 with single-stranded DNA and RNA was faster than that with duplex DNA, and produced more drug-DNA and drug-RNA adducts. Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry was used to further characterize the binding modes of BBR3464 with the DNA substrates. BBR3464 binding to different nucleic acid conformations raises the possibility that the adducts of single-stranded DNA and RNA may play a role in the different antitumor efficacies of this novel drug as compared with cisplatin.

Antineoplastic Agents↗
PubMed2003

Insights into nucleic acid conformational dynamics from massively parallel stochastic simulations.

The helical hairpin is one of the most ubiquitous and elementary secondary structural motifs in nucleic acids, capable of serving functional roles and participating in long-range tertiary contacts. Yet the self-assembly of these structures has not been well-characterized at the atomic level. With this in mind, the dynamics of nucleic acid hairpin formation and disruption have been studied using a novel computational tool: large-scale, parallel, atomistic molecular dynamics simulation employing an inhomogeneous distributed computer consisting of more than 40,000 processors. Using multiple methodologies, over 500 micro s of atomistic simulation time has been collected for a large ensemble of hairpins (sequence 5'-GGGC[GCAA]GCCU-3'), allowing characterization of rare events not previously observable in simulation. From uncoupled ensemble dynamics simulations in unperturbed folding conditions, we report on 1), competing pathways between the folded and unfolded regions of the conformational space; 2), observed nonnative stacking and basepairing traps; and 3), a helix unwinding-rewinding mode that is differentiated from the unfolding and folding dynamics. A heterogeneous transition state ensemble is characterized structurally through calculations of conformer-specific folding probabilities and a multiplexed replica exchange stochastic dynamics algorithm is used to derive an approximate folding landscape. A comparison between the observed folding mechanism and that of a peptide beta-hairpin analog suggests that although native topology defines the character of the folding landscape, the statistical weighting of potential folding pathways is determined by the chemical nature of the polymer.

Computer Simulation↗
PubMed1990

Watersoluble synthetic nucleic acid analogs--polyethyleneimine derivatives containing nucleic acid bases--conformation and interactionwith nucleic acids.

Water soluble polyethyleneimine derivatives containing nucleic acid bases were found to interact with polynucleotides, DNA, RNA. The conformational change by formation of complex was observed by CD spectra and was discussed with the hypochromicity in UV spectra. The rates of interactions between nucleic acid bases in polymers were slow as shown by UV spectra, but the conformational changes of the polynucleotides were fast as shown by CD spectra. In the case of the uracil derivative (PEI-Hse-Ura), high value of CD spectra [theta] 2.80 = -8.0 x 10(-4) for the complex with DNA might be caused by psi type conformation of DNA.

Circular Dichroism↗
PubMed1999

Resolving the discrepancies among nucleic acid conformational analyses.

Growing interest in understanding the relationship between the global folding of nucleic acids and the sequence-dependent structure of individual base-pair steps has stimulated the development of new mathematical methods to define the geometry of the constituent base-pairs. Several approaches, designed to meet guidelines set by the nucleic acid community, permit rigorous comparative analyses of different three-dimensional structures, as well as allow for reconstruction of chain molecules at the base-pair level. The different computer programs, however, yield inconsistent descriptions of chain conformation. Here we report our own implementation of seven algorithms used to determine base-pair and dimer step parameters. Aside from reproducing the results of individual programs, we uncover the reasons why the different algorithms come to conflicting structural interpretations. The choice of mathematics has only a limited effect on the computed parameters, even in highly deformed duplexes. The results are much more sensitive to the choice of reference frame. The disparate schemes yield very similar conformational descriptions if the calculations are based on a common reference frame. The current positioning of reference frames at the inner and outer edges of complementary bases exaggerates the rise at distorted dimer steps, and points to the need for a carefully defined conformational standard.

Algorithms↗
PubMedDate not supplied

[Semiempirical calculation of the relation of the interaction energy between complementary pairs of nitrogenous bases to nucleic acid conformational parameters].

The calculations of interaction energy between complementary base pairs of nucleic acids in the function of 5 variables determining parameters of double helix (Arnott's parameters) have been carried out by the method of atom-atom potential functions. Four of these parameters are essential in the case of mutual positions of bases corresponding to conformational A-family, and only two parameters (the distance between pairs along helical axis and the angle of rotation around this axis)--in the case of B-family. Positions of the interaction energy minima over each of the essential variables are close to experimentally determined parameters. The interaction energy minima are more pronounced for A-family conformations. The positions of minima in this case are determined by dispersion and short range repulsion energy.

Adenine↗
PubMed1997

Selective multiple labeling strategy to obtain accurate NMR parameters for nucleic acids. Conformational analysis around the glycosidic bond.

A systematic synthesis of pyrimidine nucleosides with 13C-labels only at specific atoms in both the base and sugar moieties has been developed in order to obtain conformational information about the glycosidic bond through measurement of the accurate vicinal coupling constants between H1' and C2/C6. For this purpose, 13C labels at three positions, namely C1', C2, and C6, are essential. We have synthesized selectively multiply labeled nucleosides, such as [2, 1'-13C2]-thymidine, [2, 1'-13C2]-2'-deoxycytidine, [6, 1'-13C2]-thymidine, and [6, 1'-13C2]-2'-deoxycytidine. These nucleosides will be useful to determine the relative orientation of the base and sugar moieties.

Carbon Isotopes↗
PubMed2003

Global mapping of nucleic acid conformational space: dinucleoside monophosphate conformations and transition pathways among conformational classes.

A global conformational space of 6253 dinucleoside monophosphate (DMP) units consisting of RNA and DNA (free and protein/drug-bound) was 'mapped' using high resolution crystal structures cataloged in the Nucleic Acid Database (NDB). The torsion angles of each DMP were clustered in a reduced three-dimensional space using a classical multi-dimensional scaling method. The mapping of the conformational space reveals nine primary clusters which distinguish among the common A-, B- and Z-forms and their various substates, plus five secondary clusters for kinked or bent structures. Conformational relationships and possible transitional pathways among the substates are also examined using the conformational states of DNA and RNA bound with proteins or drugs as potential pathway intermediates.

Algorithms↗
PubMed1989

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.

DNA↗
PubMed1982

The electrostatic field of DNA: the role of the nucleic acid conformation.

Calculations of the electrostatic field of DNA in two very different double helical conformations, A and Z, are reported and compared with the results previously obtained for B-DNA. Striking contrasts between these fields and the associated electrostatic potentials are brought into evidence. One of the major differences is that while the deepest potentials are generally located in the grooves of DNA, the strongest fields are associated with the phosphate groups. The results of screening the nucleic acids by counterions are also presented.

DNA↗