Comparative molecular field analysis property calculations

Partial Least Squares (PLS) regression (Section 35.7) is one of the more recent advances in QSAR which has led to the now widely accepted method of Comparative Molecular Field Analysis (CoMFA). This method makes use of local physicochemical properties such as charge, potential and steric fields that can be determined on a three-dimensional grid that is laid over the chemical stmctures. The determination of steric conformation, by means of X-ray crystallography or NMR spectroscopy, and the quantum mechanical calculation of charge and potential fields are now performed routinely on medium-sized molecules [10]. Modem optimization and prediction techniques such as neural networks (Chapter 44) also have found their way into QSAR. 

Another class of 3D descriptors is molecular interaction field (MIF) descriptors, with its well-known example of Comparative Molecular Field Analysis (204,205) (CoMFA). In CoMFA, the steric and electrostatic fields are calculated for each molecule by interaction with a probe atom at a series of grid points surrounding the aligned molecules in 3D space. These interaction energy fields are correlated with the property of interest. The 3D nature of the CoMFA technique provides a convenient tool for visualization of the significant features of the resulting models. 

Nair A, Jayatilleke P, Wang X, Miertus S, Welsh WJ. Computational studies on tetrahydropyrimidine-2-one (THP) HIV-1 protease inhibitors Improving 3D-QSAR comparative molecular field analysis (CoMFA) models by inclusion of calculated inhibitor- and receptor-based properties. J Med Chem 2000 45 973-83. 

Comparative Molecular Field Analysis The basic idea of Comparative Molecular Field Analysis developed by R.D. Cramer et al. (Tripos CoMFA ) is that a suitable sampling of the steric and electrostatic field around a ligand molecule may provide all the information necessary for explaining its biological property in a 3D-QSAR. The steric and electrostatic contributions to the total interaction energy between the ligand and a chosen probe are calculated... 

Once calculated, the molecular interaction field maps can be visually compared and studied. However, problems arise when a number of molecules are studied at the same time. In this case, a simple graphics analysis and visualization is not sufficient to provide the necessary information to understand the observed trend in the biological properties of a series of compounds. In such a case, appropriate chemometric tools may be extremely useful in order to condense and extract hidden information. 

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