discovery of intramolecular signal transduction network based on a new protein dynamics model of energy dissipation发现分子内信号转导网络基于一种新的蛋白质能量耗散的动力学模型.pdfVIP

Discovery of Intramolecular Signal Transduction Network Based on a New Protein Dynamics Model of Energy Dissipation 1,2 2 1 Cheng-Wei Ma , Zhi-Long Xiu , An-Ping Zeng * 1 Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology, Hamburg, Germany, 2 School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China Abstract A novel approach to reveal intramolecular signal transduction network is proposed in this work. To this end, a new algorithm of network construction is developed, which is based on a new protein dynamics model of energy dissipation. A key feature of this approach is that direction information is specified after inferring protein residue-residue interaction network involved in the process of signal transduction. This enables fundamental analysis of the regulation hierarchy and identification of regulation hubs of the signaling network. A well-studied allosteric enzyme, E. coli aspartokinase III, is used as a model system to demonstrate the new method. Comparison with experimental results shows that the new approach is able to predict all the sites that have been experimentally proved to desensitize allosteric regulation of the enzyme. In addition, the signal transduction network shows a clear preference for specific structural regions, secondary structural types and residue conservation. Occurrence of super-hubs in the network indicates that allosteric regulation tends to gather residues with high connection ability to collectively facilitate the signaling process. Furthermore, a new parameter of propagation coefficient is defined to determine the propagation capability of residues within a signal transduction network. In conclusion,