Title :
Probabilistic Model Checking Analysis of Palytoxin Effects on Cell Energy Reactions of the Na+/K+-ATPase
Author :
Braz, Fernando A. F. ; Cruz, Jader S. ; Faria-Campos, Alessandra C. ; Campos, Sergio V. A.
Author_Institution :
Dept. of Comput. Sci., Univ. Fed. de Minas Gerais, Belo Horizonte, Brazil
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.
Keywords :
biochemistry; biomembrane transport; brain; diseases; enzymes; medical disorders; molecular biophysics; positive ions; potassium; probability; sodium; toxicology; ATP deficiencies; K+; Na+; PTX action inhibition; animal cells; biological systems; brain disorders; cell energy reactions; cell transport systems; disease treatment; drugs; heat maps; ion exchange; kinetic model; palytoxin toxin interaction effects; plasma membrane; probabilistic model checking analysis; pump states; sodium-potassium ion-ATPase; transmembrane ionic transport systems; Biological system modeling; Brain modeling; Computational modeling; Drugs; Model checking; Probabilistic logic; Probabilistic model checking; palytoxin.; sodium-potassium pump; systems biology;
Journal_Title :
Computational Biology and Bioinformatics, IEEE/ACM Transactions on
DOI :
10.1109/TCBB.2013.97