What it takes to understand and cure a living system: Computational systems biology and a systems biology-driven pharmacokinetics- pharmacodynamics platform

Maciej Swat, Szymon M. Kiełbasa, Sebastian Polak, Brett Olivier, Frank J. Bruggeman, Mark Quinton Tulloch, Jacky L. Snoep, Arthur J. Verhoeven, Hans V. Westerhoff

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The utility of model repositories is discussed in the context of systems biology (SB). It is shown how such repositories, and in particular their live versions, can be used for computational SB: we calculate the robustness of the yeast glycolytic network with respect to perturbations of one of its enzyme activities and one transport system. The robustness with respect to perturbations in the key enzyme phosphofructokinase is surprisingly large. We then note the upcoming convergence of pharmacokinetics-pharmacodynamics (PK-PD) and bottom-up SB. In PK alone, quite a few one-, two- or more compartment models provide valuable initial guesses and insights into the absorption, distribution, metabolism and excretion of particular drugs. These models are phenomenological however, forbidding implementation of molecule-based tools and network information. In order to facilitate a fruitful synergy between SB and PK-PD, and between PK and PD, we present a new platform that combines standard phenomenological models used in the PK/PD field with mechanism-based SB models and approaches. © 2010 The Royal Society.
    Original languageEnglish
    Pages (from-to)16-23
    Number of pages7
    JournalInterface Focus
    Volume1
    Issue number1
    DOIs
    Publication statusPublished - 6 Feb 2011

    Keywords

    • Biology
    • Computational
    • Pharmacodynamics
    • Pharmacokinetics
    • Systems

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