The functional role of the hemoglobin-water interface

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-0) can be stabilized relative to the deoxy R-state (R-0) 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.

Automated summary

This article provides a summary of the physiological relevance of the interface between hemoglobin and its environment, with a focus on water. In vitro, in vivo, and computational experiments are summarized and discussed. The results suggest that the stability of the deoxy T-state can be affected by the hydrophobic effect, which has implications for protein stability under physiological conditions. Molecular simulations also provide insights into the Perutz model for Hb function. The challenges and potential future directions for computational studies in crowded environments are also briefly mentioned.