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bioRxiv · 10.1101/712257

Drug target discovery via network modeling: a mathematical model of the E. coli folate network response to trimethoprim

Jalli, I. S.·Lunt, S.·Xu, W.·Lopez, C.·Contreras, A.·Wilmot, C.-S.·Nijhout, F.
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Abstract

The antibiotic trimethoprim targets the bacterial dihydrofolate reductase enzyme and subsequently affects the entire folate network. We present an expanded mathematical model of trimethoprims 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.

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Jalli, I. S., Lunt, S., Xu, W., Lopez, C., Contreras, A., Wilmot, C.-S., Nijhout, F.. 2019-07-23. Drug target discovery via network modeling: a mathematical model of the E. coli folate network response to trimethoprim. https://doi.org/10.1101/712257

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