Nucleic acid structure is a key component in understanding a number of fundamental biomedical processes including replication, transcription and regulation and in facilitating the design of a variety of anti-cancer and anti-viral drugs that interact with nucleic acids. In order to understand fully nucleic acid structures it is necessary (1) to explore more broadly to discover the conformational variabilities available to these molecules as a function of environment and sequence, and (2) to explore more deeply to understand the interactions involved in determining the various conformations. Insight is needed not only into interactions within DNA and between duplex partners but also, and possibly most importantly, with the ion and solvent environment. The program of research is dedicated both to determining the detailed crystallographic structures of unique DNA sequences and to analyzing them for specific structural/environmental motifs that will aid in our understanding and modeling of more complex systems and processes. Initially the research will focus on DNA oligomers containing predominately guanine (G) and cytosine (C), both in the left-handed Z and in the right- handed helical conformations. Emphasis will be placed on structures of duplexes large enough and with high enough resolution that they can confidently and reliably be extended to understanding the polymeric structures. Various bulge sequences will also be explored to understand how these are accommodated in a duplex structure. As the understanding of these sequences develops, other sequences will be examined, including RNAs, hairpin, triplex, tetraplex and other complex structures.
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