The long-term goal of this project is the theoretical prediction of the structural changes in DNA induced by its solution environment. Intra-helical conformation transitions will be studied in order to predict conformations for different nucleotide sequences under various environmental conditions. Calculations on short fragments will be performed and rules for assembling longer sequences by concatenating short sequences will be refined and extended to include variations in the ionic strength the solution. Inter-helical associations will be studied to develop an explanation for the energetics driving the association of double helices that occurs in the packaging of DNA in viral phage heads or in the condensed state of DNA. The ability of purely electrostatic considerations to explain the inter-helical force vs. distance curves will be examined. Models consisting of x-ray diffraction coordinates for DNA and a quantum chemically derived distribution of electronic charge will be employed with various models of the counterion environment. Optimal arrangements of hexagonally packed helices with diffuse ions and specific cross-linking ions will be considered. The contribution of """"""""hydration forces"""""""" to the inter-helical association will be evaluated. A major effort is being directed toward developing suitable computational methods to carry out the proposed objectives. The electrostatic potential function for DNA that we have been developing will be extended to include variations in the ionic strength of the environment by using Grand Canonical Monte Carlo simulations to calculate the average electric fields at DNA atoms. An electrostatic potential function will be developed to best reproduce these electric fields and prediction of the DNA ion atmosphere will be pursued using methods currently under development. Simulations of the steady-state ionic distribution and the relaxation of the three-dimensional atmosphere of 150 base pair fragments in an electric field will be performed and results will be compared with electric dichroism studies of others allowing for interpretation of these experiments in terms of DNA solution structures. Maps of the ionic flux and the polarization of the ion atmosphere will be constructed.
