Deconstructing thermodynamic parameters of a coupled system from site-specific observables
Deconstructing thermodynamic parameters of a coupled system from site-specific observables
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DOI：
10.1073/pnas.1003609107
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发表时间：
2010-11-02
影响因子：
11.1
通讯作者：
Chanda, Baron
中科院分区：
文献类型：
--
作者：
Chowdhury, Sandipan;Chanda, Baron
协同相互作用介导蛋白质分子结构域之间的信息传递，是蛋白质功能和调节的主要决定因素。普遍的理论，以了解热力学起源的协同性已经发展到再现的复杂行为的全球热力学观察，如配体结合或酶的活性。然而，在大多数情况下，一个单一的全球可观测量的测量不能唯一地定义所有的条款，充分描述系统的能量。在这里，我们建立了一个理论基础，分析蛋白质热力学使用特定位点的信息。我们的治疗涉及提取与结构单元相关的位点特异性参数（定义为chi值）。我们证明，在限制条件下，chi值与直接相互作用项与观察下的结构单元和其固有的活化能。我们还介绍了一个网站的特定的相互作用能项（chi（diff）），这是一个功能的直接相互作用能的网站与系统中的每一个其他网站。当结合定点诱变和其他分子水平的扰动，分析卡值的特定位点的观测值可能提供有价值的见解蛋白质热力学和结构。
Cooperative interactions mediate information transfer between structural domains of a protein molecule and are major determinants of protein function and modulation. The prevalent theories to understand the thermodynamic origins of cooperativity have been developed to reproduce the complex behavior of a global thermodynamic observable such as ligand binding or enzyme activity. However, in most cases the measurement of a single global observable cannot uniquely define all the terms that fully describe the energetics of the system. Here we establish a theoretical groundwork for analyzing protein thermodynamics using site-specific information. Our treatment involves extracting a site-specific parameter (defined as chi value) associated with a structural unit. We demonstrate that, under limiting conditions, the chi value is related to the direct interaction terms associated with the structural unit under observation and its intrinsic activation energy. We also introduce a site-specific interaction energy term (chi(diff)) that is a function of the direct interaction energy of that site with every other site in the system. When combined with site-directed mutagenesis and other molecular level perturbations, analyses of chi values of site-specific observables may provide valuable insights into protein thermodynamics and structure.