Department of Chemistry, University of Basel, Klingelbergstrasse 80, CH-4056, Basel, Switzerland; Department of Chemistry, Brown University, Providence RI, USA.
Department of Chemistry, Harvard University, USA; Laboratoire de Chimie Biophysique, ISIS, Université de Strasbourg, 67000, Strasbourg, France.
Mol Aspects Med. 2022 Apr;84:101042. doi: 10.1016/j.mam.2021.101042. Epub 2021 Oct 29.
The interface between hemoglobin (Hb) and its environment, in particular water, is of great physiological relevance. Here, results from in vitro, in vivo, and computational experiments (molecular dynamics simulations) are summarized and put into perspective. One of the main findings from the computations is that the stability of the deoxy, ligand-free T-state (T) can be stabilized relative to the deoxy R-state (R) only in sufficiently large simulation boxes for the hydrophobic effect to manifest itself. This effect directly influences protein stability and is operative also under physiological conditions. Furthermore, molecular simulations provide a dynamical interpretation of the Perutz model for Hb function. Results from experiments using higher protein concentrations and realistic cellular environments are also discussed. One of the next great challenges for computational studies, which as we show is likely to be taken up in the near future, is to provide a molecular-level understanding of the dynamics of proteins in such crowded environments.
血红蛋白（Hb）与其环境（尤其是水）之间的相互作用具有重要的生理相关性。本文总结了来自体外、体内和计算实验（分子动力学模拟）的结果，并进行了讨论。计算的主要结果之一是，只有在足够大的模拟盒中，疏水作用才能表现出来，从而使脱氧、无配体的 T 态（T）的稳定性相对于脱氧的 R 态（R）得到稳定。这种效应直接影响蛋白质的稳定性，在生理条件下也起作用。此外，分子模拟为 Hb 功能的 Perutz 模型提供了一个动力学解释。还讨论了使用更高蛋白质浓度和现实细胞环境的实验结果。计算研究的下一个重大挑战之一是，正如我们所展示的，很可能在不久的将来进行，是提供对这种拥挤环境中蛋白质动力学的分子水平理解。
