Stabilizing non-covalent interactions of ligand aromatic moieties and proline in ligand-protein systems

Abstract

Proline, due to its conformational specificity, is known to show some unique properties and has significant functions in the tertiary structure of proteins. It was suggested that proline could have an important influence on some vital interactions in protein as well, by engaging in non-covalent stabilization interactions with some aromatic moieties. In this work, the interactions that occur between proline and some aromatic moieties in ligands were investigated by means of the density functional theory using an exchange-correlation functional capable of taking into account dispersion interactions. The obtained results showed that the stabilization energy between a properly placed proline and an aromatic moiety could be as large as 25 kJ/mol and hence be a significant factor in placing a ligand in binding site of a protein. This indicates that the error in determining the most favorable structure of ligand-protein complexes obtained by usual molecular docking experiments sometimes could be the result of neglecting this type of interactions.