My research projects are directed toward understanding the processes of macromolecular recognition. Using the techniques of x-ray crystallography, we can determine the three-dimensional structures of proteins or nucleic acid molecules of interest, identify the features which are critical for recognition, and ultimately predict what aspects to modify or target for interaction with synthetic or therapeutic molecules.
One area of study includes nucleic acid structure, in particular, synthetic oligonucleotides of more than one complete helical turn, modified protein recognition sequences, and molecules designed to adopt triple helical conformations or to mimic four-stranded junctions or cruciform structures. We are also studying nucleic acid-protein interactions based mainly on the areas of DNA recombination, modification, and repair. In these systems, comparison of the three-dimensional structure of the substrate and protein alone as well as in complex will demonstrate recognition interfaces and flexible regions which are changed as a result of interaction. Lastly, protein-protein interactions involve other types of recognition and we are examining several systems of signal transduction pathways. Information must be passed from one component to another via these interactions and knowledge of the recognition features involved will help to elucidate the mechanism and potential controls of these fundamental cellular processes.
Selected Publications:
Takahara, T., Rosenzweig, A.C., Frederick, C.A., Lippard, S.J. 1995.
Crystal Structure of Double
Stranded DNA containing the Anticancer Drug Cisplatin. Nature 377:649-52.
Anderson, A., Earp, B., and Frederick, C.A. 1996. Sequence variation
as a Strategy for Crystallizing
RNA Motifs. J. Mol. Bio. 259:696-703.
Nam, H.J., Haser, W.G., Roberts, T., Frederick, C.A. 1996. Intramolecular
Intf the Bcr-Abl
Oncoprotein. Structure 4:1105-1115.