Encoding protein-ligand interaction patterns in fingerprints and graphs.

We herewith present a novel and universal method to convert protein–ligand coordinates into a simple fingerprint of 210 integers registering the corresponding molecular interaction pattern. Each interaction (hydrophobic, aromatic, hydrogen bond, ionic bond, metal complexation) is detected on the fly and physically described by a pseudoatom centered either on the interacting ligand atom, the interacting protein atom, or the geometric center of both interacting atoms. Counting all possible triplets of interaction pseudoatoms within six distance ranges, and pruning the full integer vector to keep the most frequent triplets enables the definition of a simple (210 integers) and coordinate frame-invariant interaction pattern descriptor (TIFP) that can be applied to compare any pair of protein–ligand complexes. TIFP fingerprints have been calculated for ca. 10 000 druggable protein–ligand complexes therefore enabling a wide comparison of relationships between interaction pattern similarity and ligand or binding ...