Electrostatic properties of the nucleic acids will be determined from X- ray and neutron single crystal diffraction studies of simple nucleic acid components ranging up to minihelical dinucleotide structures. Emphasis will be on mapping the electrostatic potential, either within the crystal unit cell, or for molecules extracted from the crystal lattice. We have shown that the electrostatic potential can he experimentally determined more easily than other molecular properties such as the charge density or the electric field. With a simple structure model including only two atomic charge parameters in addition to the atomic parameters used in conventional crystal structure determinations, we expect to obtain physically meaningful maps of electrostatic potential for molecules containing at least 50 atoms. Such results will be of particular significance for the nucleic acids which have strongly ionic character and contain many polar groups. The H bonding of the bases, their stacking, the binding of counterions and polar molecules such as water, all involve interactions which are predominantly electrostatic. We will map the electrostatic potential in the voids of nucleotide crystal structures after water molecules, cations and intercalated drugs are completely or selectively removed from the pseudoatom model, and in this way we will study their binding sites. An important characteristic of this project is that experimental electrostatic potentials will be carefully cross-checked for consistency with each other and with results from simple benchmark crystal structures. We outline a new procedure for representing the electron density, the modulus of the electric field, or the electrostatic potential as the sum of contributions from spherically symmetric atomic charges. Our procedure overcomes the disadvantages inherent in fitting procedures that are based on the points of a grid and occur within a finite volume in space.
The aim i s to compile a database of atomic charges which can be conveniently incorporated as part of a standardized force field for molecular mechanics and molecular dynamics calculations.
