ALLOSTERY WITHOUT CONFORMATIONAL CHANGE - A PLAUSIBLE MODEL
ALLOSTERY WITHOUT CONFORMATIONAL CHANGE - A PLAUSIBLE MODEL
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DOI：
10.1007/bf00276625
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发表时间：
1984-01-01
影响因子：
2
通讯作者：
DRYDEN, DTF
中科院分区：
文献类型：
--
作者：
COOPER, A;DRYDEN, DTF
一个一般的模型，配体诱导的蛋白质动力学的变化可能会产生不同的结合位点之间的变构通信，即使在没有大分子构象变化。基于配体结合的统计热力学的理论分析表明，通过这种方法可以产生总计为几kJ·mol-1的合作相互作用自由能。这种效应是由大分子热波动的频率和振幅响应于配体连接的可能变化引起的，并且可以涉及所有形式的动态行为，从高度相关的低频简正模式振动到单个原子或基团的随机局部非谐运动。这种形式的动态变构主要是一种熵效应，并推导出近似表达式，这可能允许直接从实验观察，如正常模式频率和均方原子位移的变化计算真实的系统中的相互作用的大小。在不同位点的动力学过程的长程影响也可能由类似的机制介导。蛋白质和其他生物大分子可能已经进化到不仅利用平均构象状态的功能优势，而且还利用关于平均值的不可避免的热波动。
A general model is presented whereby ligand-induced changes in protein dynamics could produce allosteric communication between distinct binding sites, even in the absence of a macromolecular conformational change. Theoretical analysis, based on the statistical thermodynamics of ligand binding, shows that cooperative interaction free energies amounting to several kJ.cntdot.mol-1 may be generated by this means. The effect arises out of the possible changes in frequencies and amplitudes of macromolecular thermal fluctuations in response to ligand attachment, and can involve all forms of dynamic behavior, ranging from highly correlated, low-frequency normal mode vibrations to random local anharmonic motions of individual atoms or groups. Dynamic allostery of this form is primarily an entropy effect, and approximate expressions are derived which might allow the magnitude of the interaction in real systems to be calculated directly from experimental observations such as changes in normal mode frequencies and mean-square atomic displacements. Long-range influence of kinetic processes at different sites might also be mediated by a similar mechanism. Proteins and other biological macromolecules may have evolved to take functional advantage not only of mean conformational states but also of the inevitable thermal fluctuations about the mean.