THE EFFECT OF NUCLEIC-ACID GEOMETRY ON COUNTERION ASSOCIATION

The very high axial charge density of nucleic acids is a physical char acteristic that substantially influences the thermodynamics of virtual ly all processes in which they are involved. This arises from long ran ge electrostatic interacts between nucleic acids and the counter- and co- ions in solution so that salt concentration dramatically effects t he activities of both reactants and products. A significant contributo r to the resulting salt dependence for processes involving nucleic aci ds (e.g. ligand binding to a choice of nucleic acid substrates or a st ructural change), is the difference in arrangement of the sugar-phosph ate backbone of competing structures. This article reviews the results of a set of Grand Canonical Monte Carlo (GCMC) simulations that explo res the effect of nucleic acid geometry, varied as a function of oligo mer length and four-way junction branch length, on counterion associat ion and therefore many nucleic acid processes. These GCMC simulations, which utilize a ''primitive'' model description of the nucleic acid, are complemented by a number of simulations which numerically solve th e non-linear Poisson-Boltzmann equation utilizing detailed models for nucleic acids and proteins. Simulations of this kind are particularly useful for the study of systems that have been well characterized stru cturally, as well as thermodynamically. What is saught in the current article is insight into how an extremely general feature of DNA, namel y the geometric arrangement of its phosphate charges surrounded by an exclusion surface, might play a role in determining nucleic acid proce sses.