| Abstract: | ![]()
Interaction with the ligand binding domain of receptors for natural chemicals present one potential mechanism for the biological effects of environmental chemicals. Evidence suggests that the electrostatic interaction between the ligand and the receptor is an important component for binding to some of the relevant receptors. The presence of charged residues near the binding site suggests that the charge distribution of the free ligand may be different from the charge distribution of the ligand as it approaches the binding domain of the protein. In this study a new type of potential is computed for a series of dibenzo-p-dioxin (dioxin) ligands. This quantum mechanically computed potential results from interaction between the ligand and a trimethyl ammonium probe at a set of grid points. This interaction potential is compared with the molecular electrostatic potential computed from the wave function of the isolated ligands. Three types of local minima are found: (1) above the oxygen; (2) above the conjugated ring; and (3) above the chlorine(s). The molecular electrostatic potential emphasizes the minima associated with the chlorine atoms and, in that potential, the minima associated with the oxygen atoms disappear with chlorination. In the new potential, the minima over the oxygen atoms are maintained even in tetrachlorodioxin. As chlorination is increased the differences between the two potentials increases. The new potential shows the influence of the π-cation interaction, which is largest when there is little substitution on the ring. The presence of the probe induces a dipole component of 1 debye perpendicular to the plane of the ligand. Local minima in the interaction potential are then used as starting structures for the determination of the most stable ligand–probe complexes. The most stable structures are obtained from the minima associated with the oxygen atoms. These structures are stabilized by a hydrogen bond formation between the probe and the oxygen and the molecule is bent by 30° about the O(SINGLE BOND)O axis. For this series of molecules, the new potential retains some of the features that determine the hydrogen bond whereas the molecular electrostatic potential does not. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 673–684, 1998 |
