Molecular Similarity from Atomic Electrostatic Multipole Comparisons. Application to Anti-HIV Drugs

Abstract

A procedure is presented for the rapid calculation of the similarity between a pair of molecules based on atomic electrostatic multipole comparison. The multipoles are derived from semiempirical SCF wave functions, and the results obtained compare favorably with ab initio results. The method is illustrated by correlating the similarity and anti-HIV-1 activity of a series of azo compounds. Some generalizations are presented on the structure-activity relationships which are based on the atomic multipole distribution in the azo compounds.

Progress in the Understanding of Drug–Receptor Interactions, Part 2: Experimental and Theoretical Electrostatic Moments and Interaction Energies of an Angiotensin II Receptor Antagonist (C30H30N6O3S)

“…However, while the electrostatic potential is now widely acknowledged as a reactivity index [8,9] and is frequently reported in the literature relating to drug molecules, including some sartans, [1,3] the relevance of first and second electrostatic moments in predicting the binding mechanism in molecular recognition processes has been discussed in only a few cases [10][11][12][13] and never in the case of AII antagonists. Electric moments have the great advantage of being derivable with great accuracy from both theoretical calculations and X-ray diffraction experiments of charge density quality: [9,14] a comparison between the two estimates can reveal fundamental insights, for example, into the charge rearrangement that occurs upon crystallisation, and shows benefits and drawbacks of both methods.…”

“…[33] In this approach, E es is expressed as the sum of promolecule-promolecule, promolecule-deformation and deformation-deformation terms [Eq. (13)], where E pro-pro is the sum of the coulombic interactions between pairs of spherical atomic charge densities and can be determined as a function of their separation, E def-def is the "old" MM electrostatic component of Equation (12) arising from the deformation terms of the molecular charge distribution and E pro-def is the E pen component of Equation (12). The E def-def part was evaluated from the atom-centred multipole expansion up to the hexadecapole-hexadecapole term in the cartesian tensor formulation.…”

Electronic Energy and Multipolar Moments Characterize Amino Acid Side Chains into Chemically Related Groups

“…During the past two decades, researchers have paid a lot of attention to this definition, remarking on its importance for drug design. Other approaches based on similar ideas use electrostatic potential, electron density shape comparisons, or atomic multipole-based similarities . A common feature regarding these proposals is the vagueness concerning how they must be used for comparing submolecular regions.…”

“…Other approaches based on similar ideas use electrostatic potential, electron density shape comparisons, 8 or atomic multipole-based similarities. 9 A common feature regarding these proposals is the vagueness concerning how they must be used for comparing submolecular regions. A different approach that is based on the theory of atoms in molecules (AIM) was recently proposed, suggesting a similarity vector space composed of a given molecule's bond critical points (BCPs) as obtained from charge density analysis.…”