Abstract
The nucleic-acid bases carry structural and energetic signatures that contribute to the unique features of genetic sequences. Here, we review the connection between the chemical structure of the constituent nucleotides and the polymeric properties of DNA. The sequence-dependent accumulation of charge on the major- and minor-groove edges of the Watson–Crick base pairs, obtained from ab initio calculations, presents unique motifs for direct sequence recognition. The optimization of base interactions generates a propellering of base-pair planes of the same handedness as that found in high-resolution double-helical structures. The optimized base pairs also deform along conformational pathways, i.e., normal modes, of the same type induced by the binding of proteins. Empirical energy computations that incorporate the properties of the base pairs account satisfactorily for general features of the next level of double-helical structure, but miss key sequence-dependent differences in dimeric structure and deformability. The latter discrepancies appear to reflect factors other than intrinsic base-pair structure.
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Acknowledgment
The U.S. Public Health Service (research grant GM20861 to WKO) and the National Science Foundation (Advance Fellows Award 0137961 to MOF) have generously supported this work. We thank Dr. Suse Broyde for helpful discussions and Mr. Mauricio Esguerra for the scripts used to extract files from structural databases.
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Srinivasan, A.R., Sauers, R.R., Fenley, M.O. et al. Properties of the nucleic-acid bases in free and Watson-Crick hydrogen-bonded states: computational insights into the sequence-dependent features of double-helical DNA. Biophys Rev 1, 13–20 (2009). https://doi.org/10.1007/s12551-008-0003-2
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DOI: https://doi.org/10.1007/s12551-008-0003-2