The strong mutual interaction between highly charged polynucleotides and the ionic solution that forms their environment is an ubiquitous phenomenon, with a widely appreciated influence on nucleic acid biochemistry. However, the lack of a detailed structural picture of this environment and an inability to properly account for its influence on macromolecular behavior continues to be a major barrier to the rapidly advancing technology of macromolecular modeling. The proposed studies incorporate parallel theoretical efforts aimed at, first, the development of a quantitative description of the ionic environment of rod-like polynucleotide structures (including a detailed basis for the interpretation of experimental structural probes of these ionic distributions) and, second, the development and implementation of techniques capable of providing the necessary feedback of environmental forces on the biopolymer. The studies will focus primarily on detailed polynucleotide models with explicit account of molecular aqueous solvent effects, as more simplified models already studied are insufficiently detailed to provide the required information. The methods to be used include computer simulation via both Monte Carlo and stochastic dynamics algorithms, as well as a combination of both new and standard integral equation techniques that have been shown to provide viable routes to the information of interest, including interionic interactions in water. The merging of these parallel studies will provide a detailed account of the polynucleotide environment and provide feasible and nonempirical methods for coupling the environment with macromolecular structure and dynamics.
