Abstract
The antibiotic trimethoprim targets the bacterial dihydrofolate reductase enzyme and subsequently affects the entire folate network. We present an expanded mathematical model of trimethoprim’s action on the Escherichia coli folate network that greatly improves upon Kwon et al. (2008). The improvement upon the Kwon Model lends greater insight into the effects of trimethoprim at higher resolution and accuracy. More importantly, the presented mathematical model enables drug target discovery in a way the earlier model could not. Using the improved mathematical model as a scaffold, we use parameter optimization to search for new drug targets that replicate the effect of trimethoprim. We present the model and model-scaffold strategy as an efficient route for drug target discovery.