The major goals of this proposal are to crystallize and determine the x-ray structures of small DNA and RNA fragments both in the free state and in complexation with metals. In a collaborative venture, self complementary oligomers with varying sequences are being synthesized by Dr. Chattopadhyaya, Uppsala, Sweden and Drs. Peter Loewen and Krish Sadana at Winnipeg, Canada for our x-ray studies. The molecular structure of these systems will provide insights into the sequence specific conformational properties of DNA which is essential for a molecular-level understanding of gene expression. Besides self-complementary oligonucleotides, structural studies on non-self-complementary oligonucleotides will also be carried out to provide information on the nature of non-Watson-Crick base pairing in parallel and antiparallel chain interactions which are expected to be a significant component of the stabilization energy in tertiary structural loops and bends of nucleic acids. Excellent crystals of the calcium salt of dinucleoside monophosphate rCpA (two molecules in the asymmetric unit) and rApC have been grown and their crystal structures will be determined. This work will complement and extend our recent structure determination of a novel proflavin-CpA complex - a parallel chain dimer duplex with non-Watson-Crick base pairing. Crystallization studies on higher oligomers and also 2',5'-linked adenosine oligomers which have recently been found to occur naturally, are in progress. Structural studies are also continuing on new metal-polyphosphates, nucleoside antibiotics, protein synthesis inhibitors and nucleotide substrates. These are providing additional possibilities for metal-nucleotide interactions, the chirality and conformation of the chelate ring. In conjunction with the x-ray studies, theoretical energy calculations are carried out whenever it's found necessary.
