The goal of this project is the determination of molecular geometries of nucleic acids in atomic detail. The polymorphic secondary structures of DNA.DNA, RNA.RNA and DNA.RNA duplexes of specific repeating base sequences will be defined and refined. The primary concern is to examine the influence of base sequence on molecular morphology and to study the interactions between nucleic acids and other interactants, particularly proteins and drugs. The main experimental probe will be X-ray diffraction analysis of oriented and polycrystalline fibers and other sources of structural information from single crystals of oligonucleotides, NMR, UV and IR spectroscopy of both oligomers and polymers will be opportunistically exploited. The longterm goal is a precise description of the normal expression and regulation of the genetic information in nucleic acids and how it might be manipulated artifically.