M. Gastreich

An often encountered scenario in FBLD is experimental evidence of one or multiple fragment binders in a protein binding site. Typically, depending on quality and amount of information, subsequent steps can be divided into three classes: a) growing from these 'seeds', b) linking of two or more fragment binders, or c) merging multiple overlapping binders into a single potent lead.

To accomplish these tasks with ultimate efficiency, the software tool ReCore[1] has been developed. Based on a vast 3D fragment library, ReCore finds fragments which provide an optimal fit with the 'dangling bonds' and comply with optional filters and pharmacophore features. Based on a novel indexing technology, ReCore, in contrast to other tools targeting a similar challenge, provides its results within seconds, thus allowing interactive usage.

Synthetic access of results (which was a major weakness in the early days of de novo design) is taken care of in ReCore at three levels: during fragment creation, within query definition, and when creating the results. We will elucidate the basic principles and give examples which map onto experimental data and evolve into novel lead ideas.