Detecting drug targets with minimum side effects in metabolic networks

摘要

High-throughput techniques produce massive data on a genome-wide scale which facilitate pharmaceutical research. Drug target discovery is a crucial step in the drug discovery process and also plays a vital role in therapeutics. In this study, the problem of detecting drug targets was addressed, which finds a set of enzymes whose inhibition stops the production of a given set of target compounds and meanwhile minimally eliminates non-target compounds in the context of metabolic networks. The model aims to make the side effects of drugs as small as possible and thus has practical significance of potential pharmaceutical applications. Specifically, by exploiting special features of metabolic systems, a novel approach was proposed to exactly formulate this drug target detection problem as an integer linear programming model, which ensures that optimal solutions can be found efficiently without any heuristic manipulations. To verify the effectiveness of our approach, computational experiments on both Escherichia coli and Homo sapiens metabolic pathways were conducted. The results show that our approach can identify the optimal drug targets in an exact and efficient manner. In particular, it can be applied to large-scale networks including the whole metabolic networks from most organisms.