Carsten Detering

Lead discovery often starts from small fragment binders for which experimental evidence has been found in an active site. Development into a lead structure can involve three possible scenarios: a) to grow from these 'needles' into the depth of the pocket; b) linkage of two or more fragments into one compound with optimized potency; or c) merging two or more fragments in regions of mutual overlap.
These tasks can now be accomplished with a novel software tool, which comprises the interactive fragment based software ReCore and the well established docking engine FlexX. With ReCore, synthetically accessible compounds can be generated in seconds by using an indexed 3D fragment library on fragments or compounds that should be altered. The results can then be validated by docking without leaving the software environment.

We will elucidate the basic principles and give examples which map onto experimental data and evolve into novel lead ideas.