Structure-driven Approaches Toward Unchartered Territory

2 Structure-driven Approaches Toward Unchartered Territory 

In contrast to privileged structures, one may also deliberately search for novel features for which obviously no data exists at all. As it is unlikely that all possible bioactive features actually appear somewhere in nature or even have been found 

For specific targets, a complete enumeration of conceivable scaffolds based on previous experience may open the door toward novel, highly potent core structures, as it has been achieved in the field of BACE-1 inhibitors [106]. 

Also on the side of the diversity reagents, novel structures can be found if a systematic approach is pursued evaluation of an enumeration of 443 monocyclic ring system carrying one of 11 different functional groups (e.g., amine or boronic 

As structure drives the three-dimensional shape of compounds, another strategy toward unchartered chemical space may be shape analysis. It has been shown that most compounds fall into a limited number of shape classes [109]. However, as a molecule often can assume several energetically reasonable shapes, the use of such tools is still in its infancy. Also, shape itself will not be enough to ensure binding when electrostatic complementarity between ligand and protein is not achieved [110]. 

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