CoMFA program

Other fields than those implemented in the CoMFA program have been proposed for 3D QSAR analyses, e.g. different interaction fields calculated by the program GRID [33, 909, 910] or hydrophobic fields derived from HINT [918 — 921] (chapter 9.2). In addition, any other parameters, e.g. physicochemical properties like log P or quantum-chemical indices, may be added to the X block, if they are properly... 

The use of additional (or other) fields than the default steric and electronic fields of the original CoMFA method, together with PLS analysis or GOLPE, is quite common as a valuable extension of the CoMFA program, but it also constitutes an alternative to the relatively expensive commercial software. A combination of shape, lipophilic, steric, and electrostatic potentials in comparative analyses was termed comparative molecular potential analysis (CoMPA) [1014],... 

To refine this model qualitatively, the binding of several of these compounds was subjected to a CoMFA (Comparative Molecular Field Analysis) [39], This program examines electrostatic and steric parameters... 

The popularity of commercial programs such as Comparative Molecular Field Analysis (4,12) (CoMFA) and Catalyst (13) has limited both the evaluation and use of other QSAR methodologies. Often well-known issues associated with CoMFA and Catalyst have come to be viewed as shortcomings that simply are accepted as working limitations in a 3D-QSAR analysis. In this section we challenge this position and present 3D- and nD-QSAR methods that are able to overcome some of the issues associated with current mainstream 3D-QSAR application products. 

The GRID program [44] has been used by a number of workers as an alternative to the original CoMFA method for calculating interaction fields. An advantage of the GRID approach, apart from the large number of chemical probes... 

Beside the descriptors, further attempts have been made to encode the 3D molecular structures with functions. Such are 3D-MoRSE code [54] spectrum-like representations [55] and radial distribution functions [56]. Also, experimentally determined infrared, mass, or NMR spectra can be taken to represent a molecule [57]. Another example is comparative molecular field analysis (CoMFA) where the molecular 3D structures are optimized together with the receptor [58]. This approach is often applied in drug design or in specific toxicology studies where the receptor is known. The field of molecular descriptors and molecular representations has exploded in the recent decades. Over 200 programs for calculating descriptors and different QSAR applications are listed on web page [59]. 

Computer programs dedicated to QSAR analyses or with a QSAR component have also been used to assist in the development of suitable QSARs for various applications. Using one such package, Samuel et al. were able to generate comparative molecular field analysis (CoMFA) models to predict the cytotoxicity of a series of dibenzyltin(IV) derivatives against two human cancer cell lines, MCF-7, a mammary carcinoma, and WiDr, a colon carcinoma. 

---