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 be experimentally determined more easily than other molecular properties such as the charge density or the electric field. With a simple structure model including only a monopole 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 and cations 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 crosschecked for consistency with each other and with results from simple benchmark crystal structures. Atomic charges which are shown to give a satisfactory molecular electrostatic potential will then be candidates for inclusion as parameters in the semi-empirical force-fields required for molecular mechanics calculations. Such calculations are being used increasingly in studies of nucleic acid structure and dynamics.
