Foundations of Molecular Similarity Analysis

A theoretical foundation of molecular similarity analysis is the assumption of neighborhood behavior ,which refers to the tendency of molecules with globally similar structures to exhibit similar biological activity. The well-known similarity-property principle (SPP) of Johnson and Maggiora expresses this paradigm and promotes a holistic view of molecular structure and properties. Molecular similarity applications assume that chemical similarity can be related to biological activity in a meaningful manner. However, the success of this approach ultimately depends on the way molecular similarity is defined. 

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In this chapter we have discussed the foundations of molecular similarity analysis that are largely responsible for success or failure of similarity-based methods in the context of virtual compound screening. Furthermore, we have described how crucial underlying SAR characteristics are for molecular similarity analysis and presented a comprehensive methodological framework for the qualitative and quantitative analysis of SARs and the classification of different SAR types. 

The book begins with chemoinformatics methodology and so it ends. To close the circle, in the final chapter (Chapter 15), Jose L. Medina-Franco of the Torrey Pines Institute for Molecular Studies and Gerald M. Maggiora of the University of Arizona describe foundations of molecular similarity analysis, one of the central themes in chemoinformatics. The evaluation and quantification of molecular similarity as an indicator of activity similarity is at the core of many chemoinformatics methods and an intensely investigated research topic to this date, conceptually linked to the design and navigation of chemical feature spaces. 

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