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A different method for steric field evaluation in CoMFA improves model robustness.

Domenii publicaţii > Chimie + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Sulea, Traian; Oprea, Tudor Ionel; Muresan, Sorel; Chan, Shek Ling

Editorial: J. Chem. Inf. Comput. Sci., 37(6), p.1162-1170, 1997.


The all-grid probe Lennard-Jones 6-12 potential, typically used as steric descriptor in CoMFA, has been replaced by the vols. of van der Waals envelopes intersections between the probe-atom and the ligand mols. under investigation. The intersection vols. present a smoother distance dependence that overcomes the problems arising from formulation of a precise alignment and docking into the 3D lattice. A CoMFA-type application on a set of 78 steroid aromatase inhibitors with different grid and probe-atom characteristics suggests an improved model robustness for the new steric field in comparison with the classical 6-12 potential. Predefined cut-off and „min. sigma” values are not required. Systematic variation of the 3D lattice position leads to lower variations of cross-validated r-squared (q2LOO) at all levels of model complexity, which can be reduced with exclusion of some „interior” points. The relative simplicity and inexpensive computational demands make this steric field a promising alternative for routine CoMFA-based 3D-QSAR analyses.

Cuvinte cheie: CoMFA, Conformation (ligand), Model predictivity, Molecular association, Physicochemical simulation, QSAR (structure-activity relationship), Receptor-binding, Steric field evaluation