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Albany 2001

category image Biomolecular
Stereodynamics
SUNY at Albany
June 19-23, 2001

Using the Nonlinear Poisson-Boltzmann Equation to Study Electrostatic Properties of Nucleic Acids

Due to the highly charged nature of nucleic acids electrostatic interactions play a central role in intermolecular interactions and conformational transitions involving such biopolyelectrolytes. The properties and function of nucleic acids and its complexes with other molecules is dependent on the ionic composition of the environment. Moreover, many nucleic acids systems such as RNA need both monovalent and divalent (e.g., magnesium) ions for their structural integrity and function. For instance, it is well known that the nucleic acid conformational stability and catalytic function is affected by the presence of both monovalent and divalent cations in the solution.

Recent advances in NMR spectroscopy and X-ray crystallography has generated a huge number of detailed atomic resolution nucleic acids and its complexes with proteins, including large-scale structures such as DNA and RNA junctions, nucleosome core particle and ribosomes. In order to understand structure-function and sequence-function relationships of nucleic acids, especially large-scale structures, it is essential to obtain accurate and fast estimates of electrostatic properties under varying ionic conditions. The approach of using numerical solutions to the three-dimensional nonlinear Poisson-Boltzmann equation, which explicitly accounts for the detailed molecular structures and charge distribution of nucleic acid systems, provides a physical basis for understanding the electrostatic properties of nucleic acids in ionic solution.

First, we employ a novel hybrid boundary element and finite difference nonlinear Poisson-Boltzmann algorithm to compute different electrostatic properties such as electrostatic potential, ion concentration distribution and electrostatic free energies of nucleic acids with more than 20 base pairs. Up to the present most nonlinear Poisson-Boltzmann calculations have been limited to 20 base pairs due to memory requirements, convergence and other numerical implementation issues. Second, we consider the effect of sequence induced DNA curvature and different structural motifs (e.g., helical junctions) on the electrostatic potential and ion concentration distribution. Finally, the dependence of the electrostatic properties of various nucleic acid structures on the different molecular mechanical force field charges and radii is discussed.

Marcia O. Fenley (1), Alexander H. Boschitsch (2) and Wilma K. Olson (3)

(1) Department of Physics, Washington University, St. Louis, MO 63130; email: fenley@hbar.wustl.edu ; fax: (314) 935-6219 (2) Continuum Dynamics Inc, 34 Lexington Avenue, Ewing, NJ 08618 (3) Department of Chemistry, Rutgers, The State University of New Je