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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM039513-10
Application #
2725870
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1988-03-01
Project End
1998-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
10
Fiscal Year
1996
Total Cost
Indirect Cost
Name
Indiana University of Pennsylvania
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
073130049
City
Indiana
State
PA
Country
United States
Zip Code
15705
He, X M; Craven, B M (1993) Internal vibrations of a molecule consisting of rigid segments. I. Non-interacting internal vibrations. Acta Crystallogr A 49 ( Pt 1):10-22
Stewart, R F; Craven, B M (1993) Molecular electrostatic potentials from crystal diffraction: the neurotransmitter gamma-aminobutyric acid. Biophys J 65:998-1005
Klooster, W T; Craven, B M (1992) The electrostatic potential for the phosphodiester group determined from X-ray diffraction. Biopolymers 32:1141-54
Klooster, W T; Swaminathan, S; Nanni, R et al. (1992) Electrostatic properties of 1-methyluracil from diffraction data. Acta Crystallogr B 48 ( Pt 2):217-27
Klooster, W T; Craven, B M (1992) Structure of disodium methyl phosphate hexahydrate. Acta Crystallogr C 48 ( Pt 1):19-22
Klooster, W T; Craven, B M (1991) Electrostatic potential for O-H-O in tetragonal ammonium dihydrogenphosphate. Acta Crystallogr C 47 ( Pt 10):2196-8
Weber, H P; Craven, B M (1990) Electrostatic properties of cytosine monohydrate from diffraction data. Acta Crystallogr B 46 ( Pt 4):532-8