<br/>Improving the specificity or the affinity of a small molecule to its target protein are just two typical tasks in structure-based drug design and structure-driven developments in biotechnology. In both scenarios, a profound understanding of interatomic interactions on a geometric and an energetic level is required. The ever increasing number of high-quality protein-ligand structures provides the opportunity of gathering detailed knowledge about preferred geometrical arrangements of atoms (interaction patterns). Yet, advanced data mining-methods are needed to deduce such spatial information from the large amount of data. Ideally, these methods have to be highly adaptable with regard to the possibilities of the query design. Moreover, they need to be efficient in order to enable near-interactive use. Equally important is a result browser which presents the resulting hits and the query in a comprehensive way.<br/>In an attempt to address all these requirements we developed a new retrieval system to mine large sets of protein-ligand complexes for specific interaction patterns. Highly efficient indexing techniques and different graph-based algorithms are used to rapidly detect all occurrences of a spatial query. The queries represent a 3D constellation of atom descriptions within a protein-ligand interface. Additionally, constraints for physico-chemical properties of the protein and the ligand, e.g. the resolution, are combined with the spatial query.<br/>We are going to present an application of our new approach in a detailed analysis of different interaction patterns including specific interactions and molecular substructures demonstrating its value for various molecular design tasks.

Fast mining of adaptable interaction patterns in protein-ligand interface

251st National Meeting (2016)

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