The primary goal of the proposed research is to understand the effects that strong electrostatic fields near the surface of DNA exert on chemical reactions. The continued study of DNA-mediated catalytic reactions at the DNA surface is proposed, following prior work on acid-catalyzed reactions, with extensions to base-catalyzed reactions which involve stabilization of a hydroxy anion at the DNA surface through complexation with a divalent cation such as Mg2+. Computer modeling will employ a variety of approaches including continuum electrostatics models based on the Poisson-Boltzmann equation, and Monte Carlo and Brownian dynamics methods to explore the binding of hydrated divalent ions. Further calculations will involve molecular dynamics simulations of DNA and bound Mg2+, along with ab initio quantum chemical calculations for the evaluation of pKa shifts of hydrated Mg2+ ions induced in acidic regions of the DNA surface. These calculations will lead to an understanding of DNA-mediated chemical reactions which are relevant to drug design.
