Comparison of small molecules using promolecular electron density distribution functions

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In the frame of a promolecular representation of a molecule or a crystal, a chemical structure is considered to be the superposition of independent spherical atomic contributions. Promolecular models have often been shown as reasonable or even very good approximation levels to model electron density (ED) distributions, for example in chemical bond analysis or molecular similarity applications [1-9] even if the ED topology may differ between experimental and theoretical models especially at covalent bonds [9]. Analytical descriptions of promolecular ED distributions are either based on atomic or ionic wavefunctions [1,2,5,9], exponential functions [4], or fitted Gaussian functions [3,5,8], and are thus especially adapted to fast calculations of approximated molecular ED and their properties.
The present work is focussed on the use of PASA (Promolecular Atomic Shell Approximation) ED distributions [10] at various levels of smoothing in molecular superposition applications. Different similarity measures (overlap, Coulomb, and kinetic-type integrals, electrostatic attraction energy) are considered to generate various similarity evaluators, such as the well-known Carbó, Hodgkin-Richards, Shape Tanimoto, and Kulczynski indices.

First superpositions, applied to rigid endothiapepsin ligands, were achieved using a basic MonteCarlo/Simulated Annealing algorithm. They showed that smoothing increases the speed of the convergence to acceptable solutions. Also, distance-dependent similarity measures, such as Coulomb integrals and electrostatic energy, could lead to acceptable solutions, even when smoothing was not considered. The best results were obtained when using kinetic-type integrals and the Shape Tanimoto index, especially for the superposition of molecules with different sizes.


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Original languageEnglish
Publication statusPublished - 27 Jan 2006
EventQuantum Chemistry in Belgium : VIIth meeting - Universite de Mons-Hainaut, Belgium
Duration: 27 Jan 2006 → …


SymposiumQuantum Chemistry in Belgium : VIIth meeting
CityUniversite de Mons-Hainaut
Period27/01/06 → …


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