Holger Claußen and Sally Ann Hindle.

FlexE[1] is a docking tool that is able to take protein structure variations (e.g. protonations states) and protein flexibility into account. Both phenomena are critical for docking applications because even very slight changes in the given protein structure may prevent the prediction of the correct binding mode. Computational experiments provide evidence that docking ligands in non-native protein structures has oftentimes a much lower performance which is certainly critical e.g. in screening applications. From a set of protein conformation (ensemble), FlexE is able to select suitable partial protein configurations down to the level of individual rotamers or protonations states for a particular ligand. This selection is done the fly during the ligand placement and greatly improves over simple sequential docking into the alternative protein structures. Recent advancements and detailed results with FlexE will be presented.

[1] Claußen et al. J. Mol. Biol. (2001) 308, 377-395