Design for Specific Biological Activities

This method was applied to the design of a tripeptoid library. Experimental work on that library had been described by Zuckermann et al. who had shown that a few members of the library had high affinities for a 1-adrenergic or p-opiate receptors. The results of that published work were used as a retrospective test case to evaluate the effectiveness of Focus-2D. 

Similarity methods and their applications in virtual screening and compound collection design i.e., cherry-picking) have been widely reviewed and interested readers are referred to these publications. 

2 Diversity-based Design of General Screening Libraries 

Many reports have been published addressing various aspects of diversity analysis in the context of chemical library design and database mining. Methods have also been published to map molecules from a high-dimensional chemical space to 2D/3D space so that direct visualization of chemical similarity and diversity becomes feasible.Fow-dimensional diversity space also 

Since each molecule is represented by a vector of molecular descriptors, geometrically it is mapped to a point in a multidimensional space. The distance between two points, such as Euclidean distance, then measures the dissimilarity between the two molecules. Thus, the diversity function should be based on pair-wise distances between molecules in the subset. Another requirement for the diversity function is that, after the diversity value has been maximized by choosing dilferent subsets of molecules, the final subset that corresponds to the maximum function value is most diverse. An objective function was proposed in SAGE. In a related publication, an S-optimal function was used as the diversity function. Then, SA optimization techniques were used to optimize the diversity function by choosing different combinations of compounds or building blocks. 

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