We are investigating the specific molecular recognition of unusual DNA structures such as parallel duplexes, triplexes and quadruplexes by small molecules. There is some evidence suggesting that these types of structures may exist in vivo and they may represent unique targets for drug development. We have identified a ligand that forms a specific complex with the [d(G4T4G4)]2 quadruplex and have determined its solution structure using 2D NMR. We have published the application of DOCK to the discovery of ligands specific for the RNA major groove. Much of our structure determination work as well as DOCK-based investigations relies heavily on the use of MidasPlus. For example, visual examination of all of our structures is carried out with MidasPlus, which can provide very helpful distance and angle information for any structure. The ability to work with several different molecules is of crucial importance in evaluating the binding of one molecule to another, as in our work on ligand binding to quadruplexes and RNA duplexes.
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