H. Claußen, V. Apelt, M. Gastreich, S.A. Hindle, C. Lemmen, J. Greene

Scoring is still an open problem for docking and an all-purpose scoring function is unlikely to be found at all. Thus, target specific scoring functions are quite attractive, especially as the available data for particular targets grows. In order to create such target specific scoring functions repeated detailed analysis of docking solutions is necessary.

We present an integrated docking workflow that allows for interactive analysis of docking results and rapid prototyping of scoring functions. All docking information is stored in a database. The data can be analyzed by interactive spread sheets, from which 2D and 3D viewers can easily be launched. New scoring functions as well as filters can be defined and tested in this environment.

As a proof of concept for this approach, we performed a docking study with a set of known CDK2 inhibitors with FlexX and derived pharmacophor constraints by statistical analysis of these results. Using these constraints during docking with FlexX-Pharm[1] let to significantly improved enrichments.

[1] Hindle et al., JCAMD, 16, 129-149, 2002