Drug Design for KEGG Pathways with Answer Set Programming
Dietmar A. Seipel · 2012
A drug target is a key biomolecule in a metabolic or signalling pathway modifiable by a drug to ameliorate a specific disease condition or pathology [11].For rational drug design, sufficient information about the biomolecule is required -such as therapeutic value, pathway role, etc. -provided from databases and detailed pharmacological studies.We exploit the Kyoto Encyclopedia of Genes and Genomes (Kegg) database collection, which integrates biological compounds and enzymatic pathways [9]; this collection is part of the Japanese GenomeNet network of database and computational services for genome research and related research areas in biomedical sciences.We use answer set programming (ASP) [1] for deriving suitable minimal sets of drug targets.We encode a metabolic pathway as a disjunctive logic program P with default negation.Evaluating P with the answer set programming system DLV [10] obtains alternative sets of enzymes that could be blocked in order to inhibit the production of a target compound.Due to the problem of combinatorial explosion, drug design for metabolic networks is typically done on large computer grids, if hundreds of reactions are envolved.The combination with ASP embodies very efficient heuristics for avoiding part the problem, such that larger networks can be handled.