Close contacts between carbonyl oxygen atoms and aromatic centers in protein structures: π···π or lone-pair···π interactions?

Abstract

Lone-pair···π and, more recently, π···π interactions have been studied in small molecule crystal structures, and they are the focus of attention in some biomolecules. In this study, we have systematically analyzed 500 high-resolution protein structures (resolution ≤1.8 Å) and identified 286 examples in which carbonyl oxygen atoms approach the aromatic centers within a distance of 3.5 Å. Contacts involving backbone carbonyl oxygens are frequently observed in helices and, to some extent, in strands. Geometrical characterization indicates that these contacts have geometry in between that of an ideal π···π and a lone-pair···π interaction. Quantum mechanical calculations using 6-311++G basis sets reveal that these contacts give rise to energetically favorable interactions and, along with MD simulations, indicate that such interactions could stabilize secondary structures.