Similarity pharmacophore

Figure 16.7 (I) A graphical representation ofthe most important 3D pharmacophoric GRIND features forthe astemizole inhibitor as a reference compound [54]. (II) Similar pharmacophoric features found forthree potent P-gp inhibitors [55] as an example, these features are reported for compound 3a. The colored areas around the molecule are the GRID MIFs calculated with the DRY (yellow) and N1 (blue) probes.

Keywords diversity, similarity, pharmacophores, chemistry space, library design... 

Contents I. Introduction 34 II. Molecular Descriptors and Physicochemical Properties 36 III. Molecular Databases and Chemical Space 37 IV. Chemoinformatics in Food Chemistry 40 V. Examples of Molecular Similarity, Pharmacophore Modeling, Molecular Docking, and QSAR in Food or Food-Related Components 43 A. Molecular similarity 43 B. Pharmacophore model 47 C. QSAR and QSPR 48 D. Molecular docking 49 VI. Concluding Remarks and Perspectives 52 Acknowledgments 53 References 53... 

Figure 2.2 shows some of these methods and how they can be used in combination it also shows the outline of the following sections in this chapter. First, the concept of chemical space, including a sketch of molecular descriptors, physicochemical properties, and databases is presented. Then, a brief description of molecular similarity, pharmacophore modeling, docking, and QSAR models with the incorporation of examples of food-related components is described. These methods are mainly used to develop and analyze SAR and the resultant models can be used to perform virtual screening. Comprehensive reviews of each of these methods are described elsewhere (Alvarez and Shoichet, 2005 Leach and Willet, 2003 Varnek and Tropsha, 2008). 

Going deeper into the comparison and classification of chemical structures, a set of computational techniques are available. This section is organized to present a brief description of currently used methodologies, namely molecular similarity, pharmacophore modeling, molecular docking, and QSAR followed by application of these methods to food-related components. 

A similar pharmacophore finding was noted for early leads from the Berlex group... 

In dmg design, one must look at other properties of the molecules, and in this case the possibilities of interaction between the molecule and the biological target (e. g., an en2yme) are important. This interaction is influenced by the three-dimensional arrangement of hydrogen bond donor or acceptor groups, and of the polar or HpophiHc parts of a molecule (expressed as pharmacophores). From this point of view, two molecules are similar if they show similar pharmacophores and then they are assumed to show similar activities. 

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