Interaction fields, GRID program

Cruciani et al. [92] have developed the program Metasite for the prediction of the site of oxidative metabolism by CYP450 enzymes. Metasite uses GRID molecular interaction fields to fingerprint both structures of CYP450s (from homology models or crystal structures) and test substrates and then matches the fields. Zhou et al. [93] showed that Metasite was able to correctly predict the site(s) of metabolism 78% of the time for 227 CYP3A4 substrates. Caron et al. [94] used Metasite to predict the oxidative metabolism of seven statins. 

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... 

In principle, any method which is able to produce a molecular interaction field (MIF) could be applied to the characterization of the targets. However, almost exclusively the GRID program [19] has been used. This is due to the size of the problem which excludes the use of standard ah initio or semiempirical methods to produce interaction maps. It also reflects the many successful applications of the GRID force field in the characterization of protein active sites and the interpreta-... 

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... 

CoMFA is attractive because of its combination of understandable molecular description, statistical analysis, and graphic display of results in a computer program that is unambiguous in its application. Molecules are described with molecular interaction fields similar to those computed by GRID, statistics are computed by and cross-validation, and... 

Cruciani et al., used a dynamic physicochemical interaction model to evaluate the interaction energies between a water probe and the hydrophilic and hydrophobic regions of the solute with the GRID force field. The VolSurf program was used to generate a PLS model able to predict log Poet [51] from the 3D molecular structure. 

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