Abstract
A chalcogen bond is a nonclassical noncovalent interaction which can stabilise small-molecule crystals as well as protein structures. Here, we systematically explore the stabilising potential of chalcogen bonding in protein-ligand complexes in the Protein Data Bank (PDB).
We have found that a large fraction (23%) of complexes with a S/Se-containing ligand feature close S/Se...O/N/S contacts. Eleven non-redundant representative potential S/Se...O chalcogen-bond motifs were selected and truncated to model systems and seven more model systems were prepared by S-to-Se substitution.
These systems were then subjected to analysis by quantum chemical (QM) methods-electrostatic potential, geometry optimisation or interaction energy calculations, including solvent effects. The QM calculations indicate that chalcogen bonding does indeed play a dominant role in stabilising some of the interaction motifs studied.
We thus advocate further exploration of chalcogen bonding with the aim of potential future use in structure-based drug design.