Abstract

Beyond intra-base-pair hydrogen bonds in DNA structures: A comprehensive analysis

Institut für Molekulare Biotechnologie, Postfach 100813, D-07708 Jena, Germany

In studies on the AT tract of DNA dodecamers Nelson et al. [1] and Coll et al. [2] have identified for the first time so-called cross-strand diagonal hydrogen bonds. In addition to H-bonds in Watson-Crick base-pairs and in mismatches they represent a further type of hydrogen bonds in DNA because they connect different base-pairs. These inter-base-pair hydrogen bonds have been claimed to contribute to a particular stability and rigidity of AT sequence regions in DNA which could possibly explain what differentiates AT tracts from other sequence parts. A few further inter-base-pair H-bonds have been described in other DNA structures including AT- and non-AT regions and in a DNA-protein complex as well.
In order to gain deeper insight into the importance of this type of H-bonds for DNA structures it would be interesting to know if they are found in other structures as well and to learn more about their geometrical properties. We have used our new program HBexplore [3] to perform a systematic search for non-intra-base-pair H-bonds in a set of 202 DNA structures from the Protein Data Bank (PDB) including A-, B- and Z-DNA, other unusual DNA structures, DNA-drug and DNA-protein complexes, adopting the geometrical criteria dHA < 2.5 œÅ, dDA < 3.9 œÅ, aDHA > 90 deg, aDAA1 > 90 deg, aHAA1 > 90 deg, where d and a stand for distance and angle, D and A are the H-bond donor and acceptor atoms and A1 is the bonded neighbor of A.
HBexplore identifies in the 202 DNA structures analyzed a total number of 5776 H-bonds and among them 82 non-intra-base-pair H-bonds in 44 structures. We report distributions of geometrical H-bond parameters both for the complete set and for the non-intra-base-pair H-bonds alone and discuss other statistical properties and individual examples.
The systematic search for non-intra-base-pair H-bonds in DNA structures has identified much more bonds of this type than known so far. Even though the percentage of non-intra-base-pair H-bonds in DNA structures is very small they may have important biological implications. The results obtained can also be useful for a separation of real structure effects from effects of crystal packing and even for the identification of possible errors in structure determination.

1. Nelson, C. M., Finch, J. T., Luisi, B. V., Klug, A., Nature 1987, 330, 221-226.
2. Coll, M., Frederick, C. A., Wang, A. H. , Rich, A., Proc. Natl. Acad. U.S.A. 1987, 84, 8383-8389.
3. Lindauer, K., Bendic, C., Sühnel, J., Comput. Appl. Biosci., in press.