The dark energy of proteins comes to light: conformational entropy and its role in protein function revealed by NMR relaxation
The dark energy of proteins comes to light: conformational entropy and its role in protein function revealed by NMR relaxation
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DOI：
10.1016/j.sbi.2012.11.005
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发表时间：
2013-02-01
影响因子：
6.8
通讯作者：
Wand, A. Joshua
中科院分区：
文献类型：
--
作者：
Wand, A. Joshua
从历史上看，几乎不可能通过实验确定残留蛋白质熵对基本蛋白质活性（例如配体结合）的贡献。最近的进展阐明了采用核磁共振弛豫方法来定量确定构象熵变化在蛋白质分子识别中的作用的可能性。该方法依赖于使用快速内部蛋白质动力学作为代理。初步结果揭示了构象熵在蛋白质与配体的结合中发挥着巨大且可变的作用。构象熵在分子识别中的作用对于酶学、信号转导、变构调节和蛋白质导向药物的开发具有重要意义。
Historically it has been virtually impossible to experimentally determine the contribution of residual protein entropy to fundamental protein activities such as the binding of ligands. Recent progress has illuminated the possibility of employing NMR relaxation methods to quantitatively determine the role of changes in conformational entropy in molecular recognition by proteins. The method rests on using fast internal protein dynamics as a proxy. Initial results reveal a large and variable role for conformational entropy in the binding of ligands by proteins. Such a role for conformational entropy in molecular recognition has significant implications for enzymology, signal transduction, allosteric regulation and the development of protein-directed pharmaceuticals.