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.