Title :
Characterizing criticality of proteins by system dynamics
Author :
Li, Ru-Dong ; Liu, Lei
Author_Institution :
Key Lab. of Syst. Biol., Chinese Acad. of Sci., Shanghai, China
Abstract :
Systems biology calls for studying system-level properties of genes and proteins rather than their individual chemical/biological properties. Up to date, most studies aiming at this goal are confined to topology-based approach. However, proteins have tertiary structures and specific functional roles, especially in metabolic systems. Thus topological properties such as connectivity, path length, etc., are not good surrogates for protein properties. In the present work, we developed a method to directly assess protein system-level properties based on system dynamics and in silico knockout tests. Applying the method to E. coli central carbon metabolic system, we found that transaldolase and transketolase-b had great impact on the system in terms of both system states and dynamical stability, while glucose-6-phosphate isomerase exerted very little influence. This finding is highly consistent with experimental characterization of metabolic essentiality. We also found that enzymes could affect a distant metabolite or enzyme even greater than a close neighbor. Our work may create a new angle for evaluating protein criticality in a system.
Keywords :
biochemistry; cellular biophysics; enzymes; genetics; molecular biophysics; topology; E.coli central carbon metabolic system; chemical-biological properties; enzyme; genes; glucose-6-phosphate isomerase; metabolic systems; protein system-level properties; system dynamics; tertiary structures; topological properties; topology-based approach; transaldolase; transketolase-b; Fluctuations; Kinetic theory; Mathematical model; Orbits; Proteins; Criticality; Metabolic system; System dynamics; System-level property;
Conference_Titel :
Systems Biology (ISB), 2011 IEEE International Conference on
Conference_Location :
Zhuhai
Print_ISBN :
978-1-4577-1661-4
Electronic_ISBN :
978-1-4577-1665-2
DOI :
10.1109/ISB.2011.6033121