Distinguishing between Bioactive and Modeled Compound Conformations through Mining of Emerging Chemical Patterns
Jens Auer, Jürgen Bajorath · Journal of Chemical Information and Modeling · 2008
To systematically compare bioactive and theoretically derived compound conformations, we have analyzed 18 different sets of active small molecules with experimentally determined binding conformations and modeled conformers using a pattern recognition approach. Compound class-specific descriptor value range patterns that accurately distinguish bioactive conformations from other low-energy conformers were identified for all 18 compound classes. Discriminatory patterns were often chemically intuitive and could be well rationalized on the basis of X-ray structures of the protein-ligand complexes. Target-specific descriptor patterns can be used as filters to screen conformational ensembles for bioactive conformations.