Pharmacophores molecular interaction fields

Historically, ligand structure-based design has been the most widely used approach to the design of target-directed chemical libraries. Methods that start from hits or leads are among the most diverse, ranging from 2D substructure search and similarity-based techniques to analysis of 3D pharmacophores and molecular interaction fields (Fig. 15.2). 

Another modification of the VolSurf approach to analyze molecular interaction fields was described by Pastor et al. (2000). The same information previously been used to compute VolSurf descriptors now served to compute GRIND descriptors. In contrast to VolSurf, these descriptors capture information about pharmacophoric groups and their distances within individual molecules. These descriptors represent favorable interaction energy regions where groups... 

Triplets of Pharmacophoric Point descriptors (or TOPP descriptors) encode information on presence/absence or occurrence frequencies of 3-point pharmacophores derived from molecular interaction fields (MlFs) [Sciabola, Morao et al., 2007 Lamanna, Catalano et al, 2007]. 

Perruccio, F., Mason, J.S., Sciabola, S. and Baroni, M. (2006) FLAP 4-point pharmacophore fingerprints from GRID, in Molecular Interaction Fields, Vol. 27 (ed. G. Crudani), Wiley-VCH Verlag GmbH, Weinheim, Germany. 

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

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