Watson-Crick base pairs hydrogen bond stabilization

Just as main-chain NH 0=C hydrogen bonds are important for the stabilization of the a-helix and / -pleated sheet secondary structures of the proteins, the Watson-Crick hydrogen bonds between the bases, which are the side-chains of the nucleic acids, are fundamental to the stabilization of the double helix secondary structure. In the tertiary structure of tRNA and of the much larger ribosomal RNA s, both Watson-Crick and non-Watson-Crick base pairs and base triplets play a role. These are also found in the two-, three-, and four-stranded helices of synthetic polynucleotides (Sect. 20.5, see Part II, Chap. 16). 

Single-stranded nucleic acids can adopt structures more complex than simple stem-loops through the interaction of more widely separated bases. Often, three or more bases may interact to stabilize these structures. In such cases, hydrogen-bond donors and acceptors that ordinarily participate in Watson-Crick base pairs may participate in hydrogen bonds of nonstandard pairings. Metal ions such as magnesium ion (Mg2+) often assist in the stabilization of these more elaborate structures. 

Triple-base pairs occur when single-stranded nucleotides make hydrogen bonds with a Watson-Crick base pair. The third base may interact either within the major or the minor groove of the Watson-Crick base pair. For example, the folding of tRNA is stabilized by triple-base pairs between the junction loop and bases in the major groove of stem D. Also, a triple-base pair (UAU), between a U in a bulge and the U-A in the adjacent helix, is essential for the conformation of the binding site for human HIV protein Tat on TAR. 

The bases in nucleic acids can interact via hydrogen bonds. The standard Watson-Crick base pairs are G-C, A T (in DNA), and A U (in RNA). Base pairing stabilizes the native three-dimensional structures of DNA and RNA. 

Figure 8.7 Modification of oligonucleotides to increase stability, (a) Oligonucleotides (here shown as DNA) with a phosphodiester backbone (X = 0) are rapidly degraded by nucleases. Modification to create phosphorothioate analogs (X = S ) greatly increases half-life, (b) Peptide nucleic acids represent another DNA analog that can be used to bind with complementary sequences of oligonucleotides. Dashed lines represent hydrogen bonding which follows Watson-Crick base pairs.

Watson-Crick base pairing in complementary oligonucleotide strands keeps two rules of complementarity in both size and hydrogen-bonding patterns. Hydrophobicity and planarity in the bases also appear to be important for the stability of the double-helical structure. Designing new base pairs that vary in shape, size, and functionality has been usefiil in rmderstanding what is essential in the natural base pairing. 

DNA must be replicated with high fidelity. Each base added to the growing chain should with high probability be the Watson-Crick complement of the base in the corresponding position in the template strand. The binding of the NTP containing the proper base is favored by the formation of a base pair, which is stabilized by specific hydrogen bonds. 

Basis set effect on hydrogen bond stabilization energy estimation of the Watson-Crick type nucleic acid base pairs using medium-size basis sets single point MP2... 

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