Compound library design protein structure based

Figure 3. Approaches to cluster protein targets for screening of small molecule libraries. Currently, protein targets are clustered based on functional or amino acid sequence similarity (left). We propose to cluster proteins purely based on structural similarity of protein cores and to apply this clustering to compound library design (right).

Protein Structure Based Methods for Compound Library Design... 

The term biology-oriented synthesis (BIOS) [45] has been used to describe the design of compound libraries based on biologically relevant chemical space [46]. The areas in protein structures that participate in productive protein-ligand interactions have been, for the most part, already defined by natural products and drugs. Thus libraries inspired by natural products and other bioactive molecules are expected to have a higher probability of biologically activity than randomly synthesized molecules [47,48]. 

The advent of more accurate and rapid tools in chemoin-formatics and virtual screening makes it possible to design and synthesize a small subset of representative compounds (focused library) of a larger library. Out of various improved methods these two diversity- or structure-based approaches are frequently exercised in the design of a focused library. Once the 3D coordinates of a protein target are determined by either X-ray crystal structures or NMR, a structure-based library design is a more productive and viable approach. 

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