Ligand-based Combinatorial Design The RADDAR Approach

There has been considerable discussion on the validity of docking and scoring functions in structure-based design because of the complex issues involved such as ligand orientation, water participation, or flexibility of the target protein itself [186-190]. 

As long as the virtual structure-based screening procedure identifies compound proposals that can be realized and tested in a short period of time, the accuracy lacking in the scoring functions can be compensated and finally validated by the biophysical screening experiment itself. 

Ligand-based Combinatorial Design The RADDAR Approach 

Virtual screening on a 2-D basis is far more efficient in terms of computing time, although the information content of the resulting virtual hits is far less sophisticated than for a 3-D pharmacophore search. It is in this setting that combinatorial chemistry approaches are applied most effectively. The many interactions possible with a compound library based on virtual hits compensates for the inherent fuzziness of any prediction tool. Examples have been described where the 2-D structure of a 

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Ligand-based Combinatorial Design The RADDAR Approach 419... 

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