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变构作用:历史、概念、方法及应用概述

Allostery: An Overview of Its History, Concepts, Methods, and Applications.

作者信息

Liu Jin, Nussinov Ruth

机构信息

Department of Pharmaceutical Sciences, University of North Texas Systems College of Pharmacy, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.

Department of Chemistry, Center for Drug Discovery, Design, and Delivery (CD4), Center for Scientific Computation, Southern Methodist University, Dallas, Texas, United States of America.

出版信息

PLoS Comput Biol. 2016 Jun 2;12(6):e1004966. doi: 10.1371/journal.pcbi.1004966. eCollection 2016 Jun.

Abstract

The concept of allostery has evolved in the past century. In this Editorial, we briefly overview the history of allostery, from the pre-allostery nomenclature era starting with the Bohr effect (1904) to the birth of allostery by Monod and Jacob (1961). We describe the evolution of the allostery concept, from a conformational change in a two-state model (1965, 1966) to dynamic allostery in the ensemble model (1999); from multi-subunit (1965) proteins to all proteins (2004). We highlight the current available methods to study allostery and their applications in studies of conformational mechanisms, disease, and allosteric drug discovery. We outline the challenges and future directions that we foresee. Altogether, this Editorial narrates the history of this fundamental concept in the life sciences, its significance, methodologies to detect and predict it, and its application in a broad range of living systems.

摘要

变构的概念在过去一个世纪中不断演变。在这篇社论中,我们简要回顾变构的历史,从以玻尔效应(1904年)开始的前变构命名时代,到莫诺德和雅各布提出变构(1961年)。我们描述了变构概念的演变,从二态模型中的构象变化(1965年、1966年)到整体模型中的动态变构(1999年);从多亚基(1965年)蛋白质到所有蛋白质(2004年)。我们重点介绍了当前可用于研究变构的方法及其在构象机制、疾病和变构药物发现研究中的应用。我们概述了我们预见的挑战和未来方向。总之,这篇社论讲述了生命科学中这一基本概念的历史、其重要性、检测和预测它的方法,以及它在广泛的生命系统中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a45d/4890769/6cfbd70e7e2c/pcbi.1004966.g001.jpg

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