Nucleic acids canonical forms

Figure 1 Molecular model of a 12-base pair duplex of canonical B-form DNA. The two 12-mer strands that intertwine to form the duplex are colored separately (black and gray). Nucleic acid base pairs are stacked perpendicular to the helical axis at 3.4-A intervals (center-to-center distance), and the duplex helix repeats its spiral structure every 10 base pairs. (Figure provided by Dr. Carolyn Kanagy using the Sybyl Version 6.3 molecular modeling program from Tripos, Inc. and standard B-form DNA substructures.)...

The bases occur only in the canonical tautomeric forms [524, 525]. In both polar and nonpolar environments in the solid and solution states, the canonical forms of the bases illustrated in Fig. 15.1 are the only ones that have been observed. There is some spectroscopic NMR evidence for the occurrence of the nucleic acid bases in other tautomeric forms in solution, but only at or below the 0.01% level. This concentration is very difficult to measure, if at all possible [123, 526]. 

Polymers other than canonical DNA and RNA oligonucleotides can also form G-quadruplexes. The ability to alter the polymer backbone may result in G-quadruplexes with a variety of potential applications in supramolecular chemistry, biotechnology, and nanotechnology. In addition, studies on nucleic acid analogs may lead to insights into the structural factors that control fundamental issues about the thermodynamics and kinetics of the G-quad-ruplex motif in the parent DNA and RNA nucleic acids. 

Base triads do, of course, occur in nucleic acid triplexes. However, tetraplex structures may also contain triads and in RNA structures triads often play a crucial role. Triplexes are formed by the interaction of a third strand in the major groove of a double helix. The duplex has to be composed of a homopurine-homopyrimidine sequence (piuine - R, pyrimidine - Y). The third strand can bind in a parallel or antiparallel orientation to one of the duplex strands. In parallel orientation, a homopyrimidine third strand binds to the homopurine strand of the duplex (YRY). This leads to the two canonical triads TAT and C+GC. Protonation of C (C+) at N3 is required for the formation of two H-bonds between C and G. Therefore, parallel triplexes are pH dependent. These structures have two canonical base triads TAT and C+GC. For an antiparallel orientation of the third strand relative to the binding duplex strand, a homopruine sequence is required that binds to the homopurine strand of the duplex (RRY). This results in the canonical triads GGC, AAT and TAT, where however the TAT triad is different to the corresponding triad in parallel triplexes. In addition to these standard triads, triplexes can also accommodate non-canonical base triads. Fig. 3 shows the two canonical triads C+GC and TAT in an intra-molecular triplex consisting of a DNA duplex and... 

Recent reviews from this Laboratory provide an overview of the literature of MD simulations on DNA oligomers through 1993 (27) and theoretical and computational aspects of DNA hydration (28) and counterion atmosphere (29). References to the most recent literature can be found in (30). Experimental data for comparison with MD results are available for crystal structures in the Nucleic acids Data Bank (NDB) (31), and for NMR structure in a review by Ulyanov and James (52). The research described in this article is directed towards understanding the dynamical structure of the various right-handed helical forms of DNA, their deformations and interconversions. The canonical A and B structures of DNA are shown for reference in Figure 1. The A and B forms are distinguishable in three major ways the displacement of nucleotide base pairs from the helix axis, the inclination of base pairs with respect to the helix axis, and sugar puckers. Details on these and other structural features of DNA relevant to MD analysis is readily available (33). 

The picture of prototropic trjinsformations of the nucleic acid base tautomers will never be completed without a knowledge of inter- and intramolecular proton transfer kinetics. The most general data describing the kinetics of proton transfer are the set of temperature dependent rate constants. These data for nucleic acid bases are not yet available from either experimental or theoretical studies except the very recent paper [ 134] where the authors attempt to estimate the water assisted proton transfer rate constant for adenine. However, the calculated values of proton transfer barrier for both non-water assisted and water assisted pathways are available for the adenine, guanine and eytosine [119, 123, 134]. These data are collected in Tables 12 - 16, where, for convenience, we have defined as forward reaction the proton transfer process from the normal (canonical) to the hydroxo- (imino-) form. 

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