Results and Discussion

All chalcogen and hydrogen bonds were identified according to the procedures described in the Methods (see below). Interatomic contacts that might be considered, according to the stereochemical criteria used in this study, both hydrogen and chalcogen bonds were discarded (about 20% of the chalcogen bonds may be confused with hydrogen bonds and about 1% of the hydrogen bonds may be confused with chalcogen bonds).
Details about hydrogen and chalcogen bonds are given in Supplementary Material (Tables S1-S4 ) and are only briefly presented here.
As it can be expected, given the high frequency of occurrence – one per residue – the most common nucleophile that forms chalcogen bonds is the main-chain oxygen atom. Surprisingly, sulfur atoms act rather frequently as nucleophiles, too, despite their low frequency of occurrence in proteins [16]. As it was already observed, cysteines tend to be more frequently hydrogen donors that hydrogen acceptors in hydrogen bonds, roughly with a ratio 2:1 [4]. When the cysteine thiol group acts as a hydrogen donor, the hydrogen acceptor is often a main-chain oxygen atom and when it acts as a hydrogen acceptor, the hydrogen donor is frequently a main-chain or a water oxygen.