Low temperature dependence of protein-water interactions on barstar surface: A nano-scale modelling

The dynamics of the hydration shell of the inhibitor barstar is analysed at low temperature (300–243 K), through all-atom molecular dynamics simulations, and compared with that of bulk water. The relaxation of residence times of solvent molecules in the protein hydration shell follows a stretched exponential function exp[−(t/τ)β] with β = 0.48 ± 0.01, independent of temperature, showing that the decay process is mainly dominated by long-range molecular relaxation channels (short-range for bulk water). The percentage of water molecules exhibiting 4 hydrogen bonds, xHB4, is found to be a parameter essential for understanding some room and low temperature dependent properties of the protein hydration shell, suggesting an explanation for the unfreezing of protein hydration water as temperature decrease below 273 K. Moreover the dynamical transition that proteins and their hydration water exhibit at ~225 K can be explained by the decrease of ‘hydrogen bond defects’ in the protein hydration shell as temperature goes down. If most of those water molecules would present a tetrahedral arrangement (nearly no ‘hydrogen bond defects’), the bioactivity of proteins would be negligible. Comparison with experimental results is provided all along the work. Experimental data are quantitatively reproduced.
This work was funded by the Ministerio de Economía, Industria y Competitividad (Spain) together with the European Regional Development Fund (European Union), under common project FIS2017-87519-P. Financial support from Gobierno de Aragón (Spain), through grant E36_17R, is also acknowledged.