Nucleic acids backbone transitions

Test simulations on nucleic acid systems indicated that an max= 10.0 kcal-mor was necessary to allow for efficient nucleic acid backbone transitions and it was chosen as the highest biasing level. During replica exchange simulations five replicas with limax levels of 0 (reference replica without biasing), 1, 3, 6, and lOkcal-mol were used, which resulted in an exchange... 

A11 Tni values have been measured in phosphate buffer unless otherwise noted. If present during measurement, transition metal ions are specihed in parentheses. Ligands are shown including the linkers used to connect them to the nucleic acid backbone (e.g., the Cl of DNA and C8 of PNA) (see Fig. 4 for atom numbering information). Concentration is of duplex. 

Conformational Transitions of Nucleic Acid Backbone States. 1166... 

Multiple efforts have been made to replace phosphorous-containing linkages with sulfur-containing isosteres in the context of enzyme inhibition. In a search for nonionic transition state analog inhibitors of restriction enzymes, Blattler et al. (34) found that nucleic acid duplexes that incorporate a dimethyl sulfone in place of a phosphodiester have distorted backbones similar to those in restriction enzyme bound DNA. Chimeric DNAs that incorporate sulfone hnkages were synthesized, and depending on the location of the dimethylene sulfone hnker, either between the first AT unit or the second AT unit in the EcoRV recognition site, values were 20 nM and 120... 

The reactions of transition-metal complexes with polynucleotides generally fall into two categories (i) those involving a redox reaction of the metal complex that mediates oxidation of the nucleic acid and (ii) those involving coordination of the metal center to the sugar-phosphate backbone so as to mediate hydrolysis of the polymer. Both redox and hydrolytic reactions of metal complexes with nucleic acids have been exploited with much success in the development of tools for molecular biology. 

The reactivities of other transition-metal reagents have also been used advantageously in probing nucleic-acid stractures. As described in Section II, OSO4 reacts across the 5,6 position of accessible pyrimidines to form a cw-osmate ester. Upon treatment with piperidine, this base modification can yield scission of the sugar-phosphate backbone. Hence DNAs containing unusual local con-... 

Nucleic acids (DNA, RNA) have strong UV absorbances around 260-270 nm arising from n n transitions in the aromatic purine (A, G) and pyrimidine (U, C, T) rings of the nucleotide bases. The sugar phosphate backbone groups absorb only in the far-UV. 

Fig. 11. Nucleic acids B-DNA domain operation modes Backbone flexibilities mediating A-B transitions and intercalation geometries - an instrumentation assumed to be partially based on nonlinear excitations.31 Modified from refs. 32 and 33 (top). Water molecules connectivity pathways and Na+ counterion orientations from low to high humidity as resulting from extended Monte Carlo simulations. Modified from t ef. 34 (bottom).

The UV absorbance of nucleic acids from 200-300 nm is due exclusively to transitions of the planar purine and pyrimidine bases. The backbone begins to contribute at about 190 nm. The accessible region of the spectrum is therefore... 

The recognition and sensing of nucleic acids is another area of research that has grown rapidly in recent times. Many snch systems are based on the use of transition metal complexes, owing to their strong electrostatic interactions with the backbone of DNA and because they can additionally intercalate into DNA several examples of nonmetal-based intercalators (all organic) have been developed recently and show an excellent selectivity and... 

Varnai, P., Djuranovic, D., Lavery, R., Hartmann, B. (2002). alpha/gamma Transitions in the B-DNA backbone. Nucleic Acids Research, 30, 5398. 

It is interesting to add that simple modifications of the glycosidic angle x. which fixes the base plane with respect to the phosphodiester backbone, are also a powerful way of provoking important conformational transitions. This was demonstrated in early modeling by Olson which lead to unusual ribbon-like structures of DNA. More recently, it has been shown that such deformations are related to certain protein induced DNA deformations, leading to the so-call TA-DNA conformation and to the conformations created by extreme stretching of the double helix (see Section 3.5 and Protein-Nucleic Acid Interactions). 

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