BICLAIM library

Virtual screening in the BICLAIM library from our point of view contains five critical steps. First of all, the virtual library needs to include many diverse scaffolds and reagents for a broad decoration. Second, the query has to show high biological activity at the relevant target. Next, all molecules that were identified by the 2D feature tree search are overlaid in 3D with a hypothesis of the bioactive conformation of the query. From these overlays, the crucial selection of the scaffold for synthesis is made. Finally, the decoration of the scaffolds is designed. 

The first version of BICLAIM consisted of about 200 manually defined libraries. The structures of the library cores together with the main library information were summarized in an Excel sheet. Since then, new interesting libraries were added year by year. Synthesized combinatorial hbraries were added to the virtual space as well as new... 

FIGURE 133 Structure of virtual combinatorial libraries in BICLAIM space. Certain functional groups are detected and clipped to linking atoms to yield a virtual library core. The different attachment points are annotated with the different types of reagents that can be attached. 

BICLAIM, the chemical space of synthesizable combinatorial libraries described in Section 13.2.6, comprises about 10 virtual molecules. The enormous number of compounds precludes time consuming, systematic searches and reduces the repertoire of computational techniqnes to those tools that are explicitly optimized to handle combinatorial libraries. Complete enumeration of the entire compound set is impossible due to the time needed to perform complete enumeration and due to the storage size of the enumerated chemical space. However, even if the storage problem could be solved, there are no tools to perform a search in such a huge compound space within a satisfying time frame. Therefore, applicable tools are typically optimized to work within nn-ennmerated fragment spaces. 

The overlaps that were generated from ROCS were analyzed by visual inspection with the goal to select the most promising cores. After selection of the cores, the corresponding library was planned. Most of the BICLAIM cores arise from combinatorial chemistry synthesis protocols thus, instead of synthesizing a few representative molecules, normally 50-1000 compounds per core are synthesized. 

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