The essential influence of the solution environment, and the proximate ionic distribution in particular, on nucleic acid biochemistry is widely acknowledged. Important examples include the formation of the compact polynucleotide structures of cellular chromatin and binding and recognition processes in nucleic acid-protein complexes. However, the detailed microscopic description of this environment is only rudimentary at present. Therefore, theoretical studies of the distribution of ionic charge in polynucleotide solutions will be carried out. The first objective of this research is the description, at the molecular level, of the spatial distribution of simple salt ions around an extended polynucleotide chain and an analysis of the dependence of this distribution on small ion size and charge, as well as polyelectrolyte charge density. Corresponding studies with simple salt mixtures will be carried out in order to develop a correspondingly detailed picture of competitive ionic association. Such studies will provide a much more detailed picture of the ionic environment of polynucleotides than is presently available from experimental structural studies, such as those using NMR techniques. Further, the results will provide tests of the reliability of less detailed, but also more readily evaluated, theoretical descriptions. The studies will employ state-of-the-art statistical mechanical methods, including integral equation and computer simulation techniques; each of these is a proven approach to the study of simple electrolyte solutions. The initial polynucleotide model, that of a uniformly charged rod, has been shown by earlier work to be valuable for the interpretation of experimental data. Logical refinements of the model to include a more realistic polyelectrolyte charge distribution, polymer flexibility, and an accurate treatment of solvent effects will be pursued. The results will elucidate fundamental aspects of the molecular solution structure which underlie polynucleotide conformation and polynucleotide interactions with nucleic acids and polypeptides and will provide necessary elements for the longer term continued refinement of quantitative models for such interactions.
