Evolution and Limitations of the QSAR Paradigm

In the last three decades, three variants of a predictive drug design paradigm have come upon the scene, which are called collectively quantitative 

The second variant of QSAR is the use of actual structural descriptors, such as molecular orbital indices or topological codes, to define numerically the structure of a molecule and to find linear relationships with numerical biological data (Kier and Hall, 1976, 1992). 

The third variant, the most recent one, was born from the recognition of the importance of the three-dimensional structure of drugs (Cohen, 1985), and has evolved to three-dimensional QSAR (3D-QSAR). Comparative molecular field analysis (CoMFA) is to date the most sophisticated tool in 3D-QSAR (Cramer et al., 1988 Gaillard et al., 1994). 

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