Nucleic acid conformational analysis

Ogata et al. attacked the same nucleic acid conformation problem, but replaced the buildup scheme of Lucasius with a local filter that is equivalent to the use of a rotamer library. In both cases, these methods must deal with the fact that this is an underconstrained problem because several of the dihedrals have no NOEs associated with them. Schuster earlier treated a simple model of RNA to predict three-dimensional (3D) conformations, using a variant on a spin-glass Hamiltonian as his fitness function. The simple model used allowed for the analysis of the complexity of the fitness landscape, couched in terms of the genotype-to-phenotype mapping. 

Abstract. A model of the conformational transitions of the nucleic acid molecule during the water adsorption-desorption cycle is proposed. The nucleic acid-water system is considered as an open system. The model describes the transitions between three main conformations of wet nucleic acid samples A-, B- and unordered forms. The analysis of kinetic equations shows the non-trivial bifurcation behaviour of the system which leads to the multistability. This fact allows one to explain the hysteresis phenomena observed experimentally in the nucleic acid-water system. The problem of self-organization in the nucleic acid-water system is of great importance for revealing physical mechanisms of the functioning of nucleic acids and for many specific practical fields. 

DNA adsorption properties were first studied using a variety of solid supports for classical analysis methods including Southern and Northern transfers, dot-blotting, colony hybridization and plaque-lifts [31,32]. Studies of the interactions between nucleic acids and nitrocellulose revealed that molecular weight, finite macromolecular conformation, ionic forces and weaker forces of attraction all play a role. DNA is retained on nitrocellulose only in... 

New techniques for data analysis and improvements in instrumentation have now made it possible to carry out stmctural and conformational studies of biopolymers including proteins, polysaccharides, and nucleic acids. NMR, which may be done on noncrystalline materials in solution, provides a technique complementary to X-ray diffraction, which requires crystals for analysis. One-dimensional NMR, as described to this point, can offer structural data for smaller molecules. But proteins and other biopolymers with large numbers of protons will yield a very crowded spectrum with many overlapping lines. In multidimensional NMR (2-D, 3-D, 4-D), peaks are spread out through two or more axes to improve resolution. The techniques of correlation spectroscopy (COSY), nuclear Overhausser effect spectroscopy (NOESY), and transverse relaxation-optimized spectroscopy (TROSY) depend on the observation that nonequivalent protons interact with each other. By using multiple-pulse techniques, it is possible to perturb one nucleus and observe the effect on the spin states of other nuclei. The availability of powerful computers and Fourier transform (FT) calculations makes it possible to elucidate structures of proteins up to 40,000 daltons in molecular mass and there is future promise for studies on proteins over 100,000... 

Tn orcTer to extend these conformational energy studies to the analysis of multi-stranded nucleic acid systems, it is necessary to devise a procedure to identify the arrangements of the polynucleotide backbone that can acconmodate double, triple, and higher order helix formation. As a first step to this end, a computational scheme is offered here to identify the double helical structures compatible with given base pairing schemes. 

Because conformational changes in RNA or short DNAs typically cause small changes in electrophoretic mobility, analysis of nucleic acid folding requires careful optimization of electrophoresis conditions. By contrast, protein—nucleic acid interactions are typically easier to analyze by native PAGE because the molecular weight and positive charge of the protein produces a relatively large shift in gel mobility. 

Presence and nature of unsaturation, especially conjugated double bonds and aromatic systems. Aqueous solutions can be used. Quantitative analysis of proteins and nucleic acids DNA conformation. 

An analysis of character and frequencies of normal vibrations and scan of relaxed potential energy surface represents two complementary approaches to investigation of conformational flexibility of pyrimidine rings in nucleic acid bases. A combined application of these approaches allows estimating population of conformations with nonplanar rings for each molecule. 

The most complete picture of conformational flexibility of pyrimidine rings in nucleic acid bases has been provided by molecular dynamics study of isolated molecules using ab initio Carr-Parinello method [45]. According to these studies, the population of planar conformation of heterocycle does not exceed 20% for thymine, cytosine, and guanine and amounts to about 30% for adenine (Table 21.4). These values are considerably smaller as compared to estimations based on vibrational frequencies mentioned above. Such difference is quite natural because in the case of vibrational analysis, only the lowest ring out-of-plane normal mode is considered. However, there are also smaller contributions of the other ring out-of-plane vibrations not included in this analysis. Therefore, such estimation should be considered as an upper limit for assessment of population of planar conformation of ring. 

Biochemical processes are among the most challenging and interesting reaction systems. Due to the nature of the constituents involved, macromolecules such as nucleic acids or proteins, the processes to be analyzed do not follow a simple physicochemical model, and their mechanism cannot be easily predicted. For example, well-known reactions for simple molecules, e.g., protonation equilibria, increase in complexity for macromolecules due to the presence of polyelectrolytic effects or conformational transitions. Because the data analysis cannot be supported in a model-fitting procedure (hard-modeling methods), the analysis of these processes requires soft-modeling methods that can unravel the contributions of the process without the assumption of an a priori model. 

Jaumot, J., Escaja, N., Gargallo, R., Gonzalez, C., Pedroso, E., and Tauler, R., Multivariate curve resolution a powerful tool for the analysis of conformational transitions in nucleic acids, Nucl. Acid Res., 30, e92, 2002. http //nar.oxfordjoumals. org/content/vol 30/issue 17/index. 

X-ray crystallographers have now determined the structures of approximately one hundred biological macromolecules — proteins, nucleic acids, and viruses — to atomic resolution. These investigations have demonstrated that, unlike synthetic polymers, the biological molecules have specific three-dimensional conformations. Indeed, all information required to specify the structure of a protein is contained in the sequence of amino acids, and therefore the structure is also implicit in the sequence of nucleotides in the DNA or RNA genome. Analysis of the structures has provided explanations of their biological functions, and has revealed that there are recurrent architectural themes in their de-sign (J, 2). 

Amidon GL, Anik S, Rubin J (1975) An energy partitioning analysis of base-sugar intramolecular C-H—O hydrogen bonding in nucleosides and nucleotides. In Sundaralingam M, Rao ST (eds) Structure and conformation of nucleic acids and protein-nucleic acid interactions. University Park Press, Baltimore, pp 729- 744... 

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