In Silico Modeling of C1 Metabolism

Santhiya Kothandaram, Prabhakar Deonikar, Mrudhuula Mohan, Vyshali Venugopal, V. A. Shiva Ayyadurai^*

Systems Biology Group, International Center for Integrative Systems, Cambridge, MA, USA.

DOI: 10.4236/ajps.2015.69144                

Abstract

An integrative computational, in silico, model of C1 metabolism is developed from molecular pathway systems identified from a recent, comprehensive systematic bioinformatics review of C1 metabolism. C1 metabolism is essential for all organisms to provide one-carbon units for methylation and other types of modifications, as well as for nucleic acid, amino acid, and other biomolecule syntheses. C1 metabolism consists of three important molecular pathway systems: 1) methionine biosynthesis, 2) methylation cycle, and 3) formaldehyde detoxification. Each of the three molecular pathway systems is individually modeled using the CytoSolve?  Collaboratory?, a proven and scalable computational systems biology platform for in silico modeling of complex molecular pathway systems. The individual models predict the temporal behavior of formaldehyde, formate, sarcosine, glutathione (GSH), and many other key biomolecules involved in C1 metabolism, which may be hard to measure experimentally. The individual models are then coupled and integrated dynamically using CytoSolve to produce, to the authors’ knowledge, the first comprehensive computational model of C1 metabolism. In silico modeling of the individual and integrated C1 metabolism models enables the identification of the most sensitive parameters involved in the detoxification of formaldehyde. This integrative model of C1 metabolism, giving its systems-based nature, can likely serve as a platform for: 1) generalized research and study of C1 metabolism, 2) hypothesis generation that motivates focused and specific in vitro and in vivo testing in perhaps a more efficient manner, 3) expanding a systems biology understanding of plant bio-molecular systems by integrating other known molecular pathway systems associated with C1 metabolism, and 4) exploring and testing the potential effects of exogenous inputs on the C1 metabolism system.

Keywords

In Silico Modeling, C1 Metabolism, CytoSolve, Computational Systems Biology, Bioinformatics, Molecular Pathway, Formaldehyde, Detoxification, Maize, Methionine Biosynthesis, Activated Methyl Cycle, Folate-Mediated Pathways

Conflicts of Interest

The authors declare no conflicts of interest.

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