Molecular similarity analysis chemical space representation

In systematic SAR analysis, molecular structure and similarity need to be represented and related to each other in a measurable form. Just like any molecular similarity approach, SAR analysis critically depends on molecular representations and the way similarity is measured. The nature of the chemical space representation determines the positions of the molecules in space and thus ultimately the shape of the activity landscape. Hence, SARs may differ considerably when changing chemical space and molecular representations. In this context, it becomes clear that one must discriminate between SAR features that reflect the fundamental nature of the underlying molecular structures as opposed to SAR features that are merely an artifact of the chosen chemical space representation. Consequently, activity cliffs can be viewed as either fundamental or descriptor- and metrics-dependent. The latter occur as a consequence of an inappropriate molecular representation or similarity metrics and can be smoothed out by choosing a more suitable representation, e.g., by considering activity-relevant physicochemical properties. By contrast, activity cliffs fundamental to the underlying SARs cannot be circumvented by changing the reference space. In this situation, molecules that should be recognized as... 

Chemoinformatics (or cheminformatics) deals with the storage, retrieval, and analysis of chemical and biological data. Specifically, it involves the development and application of software systems for the management of combinatorial chemical projects, rational design of chemical libraries, and analysis of the obtained chemical and biological data. The major research topics of chemoinformatics involve QSAR and diversity analysis. The researchers should address several important issues. First, chemical structures should be characterized by calculable molecular descriptors that provide quantitative representation of chemical structures. Second, special measures should be developed on the basis of these descriptors in order to quantify structural similarities between pairs of molecules. Finally, adequate computational methods should be established for the efficient sampling of the huge combinatorial structural space of chemical libraries. 

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