Design target-focused

W Zheng, SI Cho, A Tropsha. Rational combinatorial library design 1. Focus-2D A new approach to the design of targeted combinatorial chemical libraries. J Chem Inf Comput Sci 38 251-258, 1998. 

More recently, the focus has moved from diversity in favor of combinatorial libraries designed to target specific receptors or enzymes (12). While these single-target-focused libraries remain a key component of many drug-discovery programs, and are useful in both hit to lead and lead optimization contexts,... 

Computational models relating molecular structure and/or properties to biological activity are required for the design of both target-focused and target class combinatorial libraries based on known active ligands. These models are developed from descriptors, which encode information about molecular properties... 

Zheng, W. and Lampe, J. (2002) Combinatorial optimization approaches to the design of focused, diverse, and target class oriented libraries. Cambridge Healthtech Institute s Sixth Annual Cheminformatics, Philadelphia, PA. 

There are three major sources for a typical corporate compound collection project-specific compounds accumulated over a long period of time through medicinal chemistry efforts for various therapeutic projects, individual compounds from commercial sources, and compounds from combinatorial chemistry. In practice, compound collections are often divided into subsets, for example, the diverse subsets for general HTS and target-focused subsets (such as kinase libraries or GPCR libraries). For library design, diversity and similarity are generally built into the libraries of compounds to be synthesized and/or purchased (73). 

I believe that the Nebraska experiment is an excellent illustration of one of the main problems in doing psi experiments. We can instruct the percipients to try to use their psi to focus on designated targets, and although I think such instructions are fairly effective, they are not totally so. But because we do not know what the limits of psi are, we cannot assume that the experimenter is independent of the experiment. 

Key Words Chemical diversity compound design diversity-oriented synthesis druglike compounds molecular properties natural products rule of five structure-activity relationship target-focused compound libraries. 

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