Examining Possible Physiological Roles of Hysteretic Enzymes in Regulatory Networks

几十年来广泛的生物化学和生物物理学研究表明，蛋白质不是刚性的，而是不断波动的实体。本项目将研究观察到的慢蛋白分子内动力学在细胞调控网络动力学的背景下可能的功能作用。细胞通过相互连接的蛋白质相互作用网络调节其动力学和信号传导。生物网络有点像一个复杂的电路。它处理输入信号，做出决策，并在嘈杂的环境中发挥作用。这个探索性项目的目的是确定一般的动态特性和生理后果的典型网络图案耦合到缓慢的分子内动力学。这些图案是从现实系统中抽象出来的，有广泛的实验研究。研究人员将应用网络研究中开发的工具和概念，并进行确定性和随机模拟，以揭示蛋白质构象波动的生理功能，只有在细胞调控的背景下，通过分子和细胞动力学之间的多级耦合才能完全理解。该项目将在几个不同领域的研究人员之间建立桥梁，并为我们对生物过程的调节和效率的理解提供新的见解。后者的例子包括生物合成所需的产品，如生物燃料。拟议的研究将培养急需的多学科学生。

Decades of extensive biochemistry and biophysics studies reveal that proteins are not rigid but ever-fluctuating entities. This project will examine the possible functional roles of the observed slow protein intramolecular dynamics in the context of cell regulation network dynamics. Cells regulate their dynamics and signaling through interconnected protein interaction networks. A biological network somewhat resembles a complex electric circuit. It processes input signals, makes decisions and functions against noisy environment. This exploratory project aims to identify general dynamic properties and physiological consequences of typical network motifs coupled to slow intramolecular dynamics. These motifs are abstracted from realistic systems with extensive experimental studies available. The researchers will apply the tools and concepts developed in network studies and perform deterministic and stochastic simulations to reveal the physiological functions of protein conformational fluctuations, which can be fully understood only in the context of cell regulation through multi-level coupling between molecular and cellular dynamics.This project will bridge researchers in several different fields, and add generate new insights into our understanding of the regulation and efficiency of biological processes. Examples of the latter include biosynthesis of desirable products such as biofuels. The proposed research will train highly needed multi-disciplinary students.