a new concept to reveal protein dynamics based on energy dissipation一个新概念揭示蛋白质动力学基于能量耗散.pdfVIP

A New Concept to Reveal Protein Dynamics Based on 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 Protein dynamics is essential for its function, especially for intramolecular signal transduction. In this work we propose a new concept, energy dissipation model, to systematically reveal protein dynamics upon effector binding and energy perturbation. The concept is applied to better understand the intramolecular signal transduction during allostery of enzymes. The E. coli allosteric enzyme, aspartokinase III, is used as a model system and special molecular dynamics simulations are designed and carried out. Computational results indicate that the number of residues affected by external energy perturbation (i.e. caused by a ligand binding) during the energy dissipation process shows a sigmoid pattern. Using the two-state Boltzmann equation, we define two parameters, the half response time and the dissipation rate constant, which can be used to well characterize the energy dissipation process. For the allostery of aspartokinase III, the residue response time indicates that besides the ACT2 signal transduction pathway, there is another pathway between the regulatory site and the catalytic site, which is suggested to be the b15-aK loop of ACT1. We further introduce the term ‘‘protein dynamical modules’’ based on the residue response time. Different from the protein structural modules which merely provide information about the stru