TIde: a software for the systematic scanning of drug targets in kinetic network models

We show an algorithm that systematically tests the influence of activators and inhibitors of different type and strength acting at different positions in the network. The effect on a quantity to be selected (e.g. a steady state flux or concentration) is calculated. Moreover, combinations of two inhibitors or one inhibitor and one activator targeting different network positions are analysed. Furthermore, we present TIde (Target Identification), an open source, platform independent tool to investigate ordinary differential equation models in the common systems biology markup language format. It automatically assigns the respectively altered kinetics to the inhibited or activated reactions, performs the necessary calculations, and provides a graphical output of the analysis results. For illustration, TIde is used to detect optimal inhibitor positions in simple branched networks, a signalling pathway, and a well studied model of glycolysis in Trypanosoma brucei.Using TIde, we show in the branched models under which conditions inhibitions in a certain pathway can affect a molecule concentrations in a different. In the signalling pathway we illuminate which inhibitions have an effect on the signalling characteristics of the last active kinase. Finally, we compare our set of best targets in the glycolysis model with a similar analysis showing the applicability of our tool.In the current pharmaceutic development new drugs are often found by screening a library of small molecular entities (SME) against so-called 'blockbuster targets' which are supposed to play a relevant role in the onset of a certain disease. The development of drugs for new targets is in most cases less interesting for a pharmaceutical company due to the fact that the research is more expensive, they fail pre-clinical trials more often and are in most cases financially less successful [1,2]. In order to increase the productivity of 'Research and Development' (R&D) when focussing on novel targets a possible