Drug‐receptor Recognition: Molecular Orientation and Dielectric Effects

Abstract

1 The orientation of ethidium and its carboxyphenyl derivative was computed at various positions around one turn of the B-DNA helical receptor. 2 Dielectric effects of solvent were included using values for the bulk constant and a dielectric vector to simulate dielectric inhomogeneities. 3 From the electrostatic energy values for the orientations, the corresponding Boltzmann distributions were obtained to assess the orientation restriction to the drug imposed by the receptor. 4 A correlation was observed between the direction of the drug molecular dipole and the local line of force generated by the receptor vector field. 5 These findings are discussed with respect to the phenomenon of drug-receptor recognition.

Drug‐receptor Recognition: Electrostatic Field Lines at the Receptor and Dielectric Effects

“…This observation is to be expected from the distancedielectric relationship used in Figure 1. Further out, that is greater than 5A, the force vectors are little affected by how the dielectric is calculated, although the magnitude of the molecular interaction energy is considerably different (Dean, 1981).…”

“…In the following paper the orientation energies of two drugs, ethidium and its carboxyphenyl derivative, have been calculated for different positions in the receptor field, mapped in this work, where rotational freedom is unhindered by atom collisions (Dean, 1981). A good correlation was found between molecular orientation and the direction of the receptor field when the drug dipole was aligned approximately anti-parallel to the field line.…”

“…The results indicate that treating the dielectric as a vector enhances the directional component of the lines of force. A subsequent paper is devoted to examining whether a correlation exists between the current findings and the computed orientation of a drug molecule approaching its receptor (Dean, 1981).…”

“…This paper is a development of previous work on electrostatic features of drug-receptor recognition (Dean & Wakelin, 1979;1980a,b) (Dean, 1981).…”