Volume 3 Supplement 1
DrugscoreMapsvisualizing similarities in protein-ligand interactions
© Koch et al; licensee BioMed Central Ltd. 2009
Published: 05 June 2009
A new approach will be presented that graphical evaluate Drugscore Fingerprints  using emergent self-organizing maps (ESOMs)  for clustering of binding geometries to identify similarities among protein-ligand interactions in data sets of protein-ligand poses. The result of the clustering shows a landscape of valleys and mountains and is easy to interpret. Similar binding geometries are clustered together within a valley surrounded by mountains. Colouring of the data points based on DrugscoreCSD ranks  or known affinity data reveals additional information.
A survey of the Wang  and the Astex Diverse Dataset  exhibits that DrugscoreMaps is useful for the evaluation of docking poses and it supports the search for the correct low energy binding mode. DrugscoreMaps combines the information about similar protein-ligand poses with the information about interaction patterns (represented by Drugscore). Clearly separated clusters with high-ranked docking poses are an indication of good binding geometries and, in contrast, a lack of clustering seems to indicate a failing of the docking procedure. Additionally, bad geometries with a high rank and situations were the scoring function fails can be identified. Furthermore, an analysis of a successfully used QSAR dataset reveals a first indication that DrugscoreMaps is also useful for visualization of structure-activity landscape within this dataset. Compared to other fingerprint based methods, DrugscoreMaps (using DrugscoreFP) integrates protein information for creating these structure-activity landscapes.
DrugscoreMaps benefits by ease of visualization. Protein-ligand similarity is included in one image that gives you a direct overview of the used dataset. One gains information about similar high-ranked docking poses and dissimilar docking poses or an overview over the structure-activity landscape without looking at all docking solutions or protein-ligand poses.
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