The strong mutual interaction between biopolymers and their solution environment exerts a widely appreciated influence on the structures and function of such macromolecules. This is particularly true of the highly charged polynucleotides. However, the inability to fully account for solvation, electrostatic interactions, and the contribution of a salt environment in the modelling of biopolyelectrolytes is one of the most conspicuous shortcomings in the area. Two major aspects of such environmental modelling will be addressed in the proposed studies. First, studies will be carried out that will provide a rigorous understanding of the abilities and limitations of alternative approximate theoretical approaches for the description of solvent- mediated ionic interactions. Second, the necessary information to rigorously test the predictions of such methods against NMR experimental data will be developed, and the tests will be executed. In order to do this incisively, benchmark simulation studies of solvent-mediated interactions for model atomic and molecular ionic systems in water will first be carried out in order to address the dependence on solvent model and on simulation procedures, such as potential truncation. The results will provide needed tests of the techniques now commonly employed in all-atom modelling of complex biopolymer systems and of the predictions of computationally convenient approximate theories for such interactions. The same data will provide a basis for evaluating NMR spin relaxation data from the models, so that the relevance of the models to real systems can be evaluated, both in relatively simple salt solutions and in DNA solutions. To further elucidate the small ion behavior in DNA solutions, the stochastic simulation of DNA solution dynamics will be pursued, with particular emphasis on the role of DNA conformation and flexibility in determining the observations in recent NMR experiments. This effort will both elucidate the informational content of the experimental data and provide further evidence regarding the relevance of models. Finally, we will focus on the computational development and theory for the environmentally induced forces on biopolyelectrolytes. The performance of the research described will provide well defined bounds on both the precision and relevance of available models and theoretical methods and delineate the viable routes for the treatment of the solution environment of polynucleotides, in particular, and biopolymers, in general.
