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Conceptual DFT properties‐based 3D QSAR: Analysis of inhibitors of the nicotine metabolizing CYP2A6 enzyme
Author(s) -
Van Damme Sofie,
Bultinck Patrick
Publication year - 2009
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.21177
Subject(s) - quantitative structure–activity relationship , computational chemistry , chemistry , homo/lumo , fukui function , steric effects , density functional theory , electron density , molecule , stereochemistry , electron , physics , organic chemistry , quantum mechanics , electrophile , catalysis
Structure‐activity relationships of 46 P450 2A6 inhibitors were analyzed using the 3D‐QSAR methodology. The analysis was carried out to confront the use of traditional steric and electrostatic fields with that of a number of fields reflecting conceptual DFT properties: electron density, HOMO, LUMO, and Fukui f − function as 3D fields. The most predictive models were obtained by combining the information of the electron density with the Fukui f − function ( r 2 = 0.82, q 2 = 0.72), yielding a statistically significant and predictive model. The generated model was able to predict the inhibition potencies of an external test set of five chemicals. The result of the analysis indicates that conceptual DFT‐based molecular fields can be useful as 3D QSAR molecular interaction fields. © 2008 Wiley Periodicals, Inc. J Comput Chem 2009