Kumar Ambuj, Jernigan Robert L
Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, United States.
Front Mol Biosci. 2021 Sep 1;8:733148. doi: 10.3389/fmolb.2021.733148. eCollection 2021.
Allostery is usually considered to be a mechanism for transmission of signals associated with physical or dynamic changes in some part of a protein. Here, we investigate the changes in fluctuations across the protein upon ligand binding based on the fluctuations computed with elastic network models. These results suggest that binding reduces the fluctuations at the binding site but increases fluctuations at remote sites, but not to fully compensating extents. If there were complete conservation of entropy, then only the enthalpies of binding would matter and not the entropies; however this does not appear to be the case. Experimental evidence also suggests that energies and entropies of binding can compensate but that the extent of compensation varies widely from case to case. Our results do however always show transmission of an allosteric signal to distant locations where the fluctuations are increased. These fluctuations could be used to compute entropies to improve evaluations of the thermodynamics of binding. We also show the allosteric relationship between peptide binding in the GroEL trans-ring that leads directly to the release of GroES from the GroEL-GroES cis-ring. This finding provides an example of how calculating these changes to protein dynamics induced by the binding of an allosteric ligand can regulate protein function and mechanism.
变构通常被认为是一种与蛋白质某一部分的物理或动态变化相关的信号传递机制。在此，我们基于用弹性网络模型计算出的涨落，研究配体结合后整个蛋白质涨落的变化。这些结果表明，结合会降低结合位点处的涨落，但会增加远程位点处的涨落，不过并非完全补偿的程度。如果存在完全的熵守恒，那么只有结合焓才重要，而熵不重要；然而情况似乎并非如此。实验证据还表明，结合能和熵可以相互补偿，但补偿程度因情况而异。不过我们的结果始终显示变构信号会传递到涨落增加的远处位置。这些涨落可用于计算熵，以改进对结合热力学的评估。我们还展示了GroEL反式环中肽结合与GroES从GroEL - GroES顺式环直接释放之间的变构关系。这一发现提供了一个例子，说明计算变构配体结合引起的蛋白质动力学变化如何能够调节蛋白质功能和机制。
