Probabilistic Model Checking Analysis of Palytoxin Effects on Cell Energy Reactions of the Na+/K+-ATPase

Authors:
Fernando A. F. Braz;Jader S. Cruz;Alessandra C. Faria-Campos;Sergio V. A. Campos
Affiliations:
Universidade Federal de Minas Gerais, Belo Horizonte;Universidade Federal de Minas Gerais, Belo Horizonte;Universidade Federal de Minas Gerais, Belo Horizonte;Universidade Federal de Minas Gerais, Belo Horizonte
Venue:
IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB)
Year:
2013

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Abstract

Probabilistic model checking (PMC) is a technique used for the specification and analysis of complex systems. It can be applied directly to biological systems which present these characteristics, including cell transport systems. These systems are structures responsible for exchanging ions through the plasma membrane. Their correct behavior is essential for animal cells, since changes on those are responsible for diseases. In this work, PMC is used to model and analyze the effects of the palytoxin toxin (PTX) interactions with one of these systems. Our model suggests that ATP could inhibit PTX action. Therefore, individuals with ATP deficiencies, such as in brain disorders, may be more susceptible to the toxin. We have also used heat maps to enhance the kinetic model, which is used to describe the system reactions. The map reveals unexpected situations, such as a frequent reaction between unlikely pump states, and hot spots such as likely states and reactions. This type of analysis provides a better understanding on how transmembrane ionic transport systems behave and may lead to the discovery and development of new drugs to treat diseases associated to their incorrect behavior.