Mechanical processes are involved at many stages of the development of living cells, and often external forces applied to a biomolecule result in its unfolding. Although our knowledge of the unfolding mechanisms and the magnitude of the forces involved has evolved, the role that water molecules play in the mechanical unfolding of biomolecules has not yet been fully elucidated. To this end, we investigated with steered molecular dynamics simulations the mechanical unfolding of dystrophin's spectrin repeat 1 and related the changes in the protein's structure to the ordering of the surrounding water molecules. Our results indicate that upon mechanically induced unfolding of the protein, the solvent molecules become more ordered and increase their average number of hydrogen bonds. In addition, the unfolded structures originating from mechanical pulling expose an increasing amount of the hydrophobic residues to the solvent molecules, and the uncoiled regions adapt a convex surface with a small radius of curvature. As a result, the solvent molecules reorganize around the protein's small protrusions in structurally ordered waters that are characteristic of the so-called “small-molecule regime,” which allows water to maintain a high hydrogen bond count at the expense of an increased structural order. We also determined that the response of water to structural changes in the protein is localized to the specific regions of the protein that undergo unfolding. These results indicate that water plays an important role in the mechanically induced unfolding of biomolecules. Our findings may prove relevant to the ever-growing interest in understanding macromolecular crowding in living cells and their effects on protein folding, and suggest that the hydration layer may be exploited as a means for short-range allosteric communication.
Bibliographical noteFunding Information:
This work was supported in part by the National Science Foundation grant no. MCB-1616854 to A.C. The authors acknowledge the Minnesota Supercomputing Institute at the University of Minnesota for providing resources that contributed to the research results reported within this work. URL: https://www.msi.umn.edu .
This work was supported in part by the National Science Foundation grant no. MCB-1616854 to A.C. The authors acknowledge the Minnesota Supercomputing Institute at the University of Minnesota for providing resources that contributed to the research results reported within this work. URL: https://www.msi.umn.edu.
© 2020 Biophysical Society
PubMed: MeSH publication types
- Journal Article
- Research Support, U.S. Gov't, Non-P.H.S.