Protein hydration shell formation: Dynamics of water in biological systems exhibiting nanoscopic cavities

This work explores the singular scenarios emerging from nanoscopic cavities, located in aqueous solutions, that include biomolecules and, as a consequence, the process of biomolecule hydration shell formation. The research presents a nano-scale study, performed in various systems related with protein-water solutions, using all-atoms molecular dynamics simulations. This research shows that if a protein falls within an empty nanoscopic cavity located in an aqueous solution, it will take a time, with a magnitude significant for biological processes, to rebuild its whole network of hydrogen bonds with the solvent molecules. During that protein isolation time the dynamics of the biomolecule, and therefore the corresponding bioactivity, will be seriously compromised. In the case of the protein barstar (radius of gyration of 1.17 nm) located in the centre of cavities with radius r from 2.5 to 4.5 nm, and solvent diffusion coefficients for bulk and physiologic water (2.4 and 1.5 mu m(2)/ms, respectively), that time is found to be of the order of tens-hundreds of picoseconds, a significant temporal range concerning the dynamics and bioactivity of proteins. On the other hand, the dynamics of formation of the inner protein hydration shell has been followed using an atomic view. The required time has been found to decrease with r, as the network of water molecules approaching the biomolecule resembles that of the biological water corresponding to that biomolecule. That resemblance increases as those water molecules have previously been in close contact with the protein. The dynamics of those systems has been modelled using a two states model. Isolated bulk water is taken as reference for the computer simulations. Comparison with experimental data is also provided. (C) 2021 The Author(s). Published by Elsevier B.V.