Cytochrome CoMFA

A widely used 3-D QSAR method that makes use of PLS is comparative molecular field analysis (CoMFA), in which a probe atom is used to calculate the steric and electronic fields at numerous points in a 3D lattice within which the molecules have been aligned. Poso et al. [56] used the technique to model the binding of coumarins to cytochrome P450 2A5, with similar results to those obtained by Bravi and Wikel [55]. Shi et al. [57] used it to model the estrogen receptor binding of a large diverse set of compounds, and Cavalli et al. [58] used it to develop a pharmacophore for hERG potassium... 

Comparative molecular Leld analysis (CoMFA) is another promising approach developed in recent years for QSAR study. CoMFA is a molecular modeling technique forthe determination of molecular stericand electrostatic force Lelds (Tripos, 1992). It has been successfully used in deriving molecular descriptors for prediction of the bioactivity of steroids (Cramer etal., 1988), molecular Lux through a polymer membrane (Liu and Matheson, 1994), and metabolism and cytochrome p450 enzyme activities (Long and V felker, 2003). 

Asikainen, A.H., Ruuskanen, J. and Tuppurainen, K.A. (2005) Alternative QSAR models for selected estradiol and cytochrome P450 ligands comparison between classical, spectroscopic, CoMFA and GRID/GOLPE methods. SAR ej QSAR Environ. Res., 16, 555-565. 

Fig. 12 41 Contour representation of key features from a CoMFA analysis of a senes of coumann substrates and inhibitors o cytochrome P glAS fPoso el al 1995] The red and blue regions indicate positions where it wnild he fnmi ahlp n id nnfnrnrnlle esperineh, fo place n p p , PfPgj, eo C - j. r k...

Cytochrome P450 2A5 and 2A6" Rigid fit CoMFA and GRID/GOLPE 0.8... 

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