It is possible to hypothesize a local structural rearrangement that transforms the chalcogen bond into a hydrogen bond, and vice versa . In other words, an oscillation from chalcogen to hydrogen bond. This would optimize the bonding requirements and decrease the entropic cost of protein folding.
It is nevertheless important to observe that the statistical analyses presented in this manuscript cannot provide a quantitative estimation of the energy associated with chalcogen and hydrogen bonds. There are in fact several limitations. For example, although the position of the hydrogen atoms is of crucial importance for defining hydrogen bonds, it is usually unknown in protein crystal structures, especially for acidic and rotatable hydrogen atoms. Moreover, without the hydrogen position, one cannot identify chalcogen bonds that might be formed along the extension of the H-S covalent bond. Moreover, chalcogen and hydrogen bonds involving aromatic rings were not considered in the present study, for the sake of simplicity, though they might participate in protein structure stabilization, by forming both chalcogen and hydrogen bonds.
Further analyses, focused on X-ray and neutron protein crystal structures at extremely high resolution might provide additional information as well as analyses of protein structures determined with alternative methods – e.g. cryo-electron crystallography and nuclear magnetic resonance in solution.