Concerning the focus of this study - the relative frequency of chalcogen
and hydrogen bonds – it is interesting to observe that hydrogen bonds
are about 40-50 times more common than chalcogen bonds (Table
1 ). This suggests that they are stronger. Not 40-50 times stronger,
obviously. This indicates that in most of the cases, the hydrogen bond
that a thiol group may form is more stable that alternative chalcogen
bond: even a small difference would produce the prevalence of hydrogen
bond, from a thermodynamic perspective. Precise estimations of the
energy of these interactions is unfortunately impossible, based on
statistical observations, since the probability density functions of the
energies are unknown. However, it is clear that hydrogen bonds are
stronger, on average.
Table 1 also shows that trends and tendencies evaluated by
using a non-redundant subset of the Protein Data Bank (Singledataset) or by following the RaSPDB method (raspdb_x datasets)
are nearly equivalent. This reinforces the use of the RaSPDB method,
which allows one to use a greater amount of information and to compute
estimated errors.
The trends outlined above are independent on the secondary structure or
on the degree of solvent accessibility of the cysteines.
If chalcogen and hydrogen bonds would have the same strength, one would
expect two-to-three hydrogen bonds per chalcogen bond, since the number
of hydrogen bonds that a cysteine thiol group can form is likely to be
higher than the number of chalcogen bonds that it can form
(Figure 1 ). However, the observed difference in the number of
bonds is much higher.
The interaction energy of both chalcogen and hydrogen bonds can be quite
variable. Both chalcogen and hydrogen bond have an electrostatic
component, which strongly depend on the local environment – i.e.on the local dielectric constant. Consequently, chalcogen bonds may be
stronger than hydrogen bond, in some cases.
It is interesting to observe that the presence of a hydrogen donor may
hinder, because of steric reasons, the formation of a chalcogen bond
along the extension of the C-S covalent bond. In other words, the
hydrogen donor and the nucleophile roughly compete for the same position
close to the sulfur atom (Figure 1 ).