Loutchko Dimitri, Flechsig Holger
Department of Complexity Science and Engineering, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, 277-8561, Japan.
Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.
Biophys Rev. 2020 Apr;12(2):443-452. doi: 10.1007/s12551-020-00667-8. Epub 2020 Mar 20.
Allosteric regulation is crucial for the operation of protein machines and molecular motors. A major challenge is to characterize and quantify the information exchange underlying allosteric communication between remote functional sites in a protein, and to identify the involved relevant pathways. We review applications of two topical approaches of dynamical protein modeling, a kinetic-based single-molecule stochastic model, which employs information thermodynamics to quantify allosteric interactions, and structure-based coarse-grained modeling to characterize intra-molecular couplings in terms of conformational motions and propagating mechanical strain. Both descriptions resolve the directionality of allosteric responses within a protein, emphasizing the concept of causality as the principal hallmark of protein allostery. We discuss the application of techniques from information thermodynamics to dynamic protein elastic networks and evolutionary designed model structures, and the ramifications for protein allostery.
变构调节对于蛋白质机器和分子马达的运作至关重要。一个主要挑战是表征和量化蛋白质中远程功能位点之间变构通讯背后的信息交换，并识别所涉及的相关途径。我们综述了动态蛋白质建模的两种热门方法的应用，一种基于动力学的单分子随机模型，该模型采用信息热力学来量化变构相互作用，以及基于结构的粗粒度建模，以根据构象运动和传播的机械应变来表征分子内耦合。这两种描述都解决了蛋白质内变构响应的方向性问题，强调因果关系的概念是蛋白质变构的主要标志。我们讨论了信息热力学技术在动态蛋白质弹性网络和进化设计模型结构中的应用，以及对蛋白质变构的影响。
