Site-focused libraries

Keywords Site-focused libraries, structure-based combinatorial chemistry, structure-... 

This chapter has reviewed the basic principles of computer-aided drug design, and several strategies of how it can be successfully integrated with combinatorial chemistry to develop highly effective site-focused libraries. Diversity plays a key role, as the more diverse set of compounds tested that fit the site-focused criteria, the more information is retrieved to improve the site-focused definition, which further directs the search in diversity space. In addition, if good hits are found, the information can be fed back to find compounds close in diverse space to the hit. This new paradigm for structure-based combinatorial chemistry should provide a powerful tool for rapid discovery of novel, potent lead compounds in the years to come. 

Roe D.C. Molecular diversity in site-focused libraries. In Molecular Diversity in Drug Design, Ed. Dean P.M. and Lewis R.A., Kluwer, 1999. Ch. 7. 

Different strategies for combiningdiversity and structure-based design in site-focused libraries and the DOCK-based CombiBUILD algorithm are discussed in a review (125), as an example of how lead compounds can be rapidly identified by combining diversity with structure-based design in site-focused libraries. 

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