An ab initio and data mining study on aromatic-amide interactions

The aromatic-amide interaction has been investigated by means of theoretical calculations and analyses of experimental protein structures. Ab initio calculations of the benzene-formamide model complex show that the interaction can achieve a significant stabilization energy (4.0 kcal/mol) which involves the entire amide moiety rather than only the amine and which originates mainly from dispersion and quadrupole(aromatic)-dipole(amide) electrostatic interactions. Data mining of X-ray protein structures reveals that the face-to-face orientation is the preferred configuration; more than four energetically favored aromatic(Phe)-amide interaction configurations occur in protein structures in nature, each corresponding to 1.0-4.0 kcal/mol stabilization energy. This study demonstrates that the aromatic-amide interaction is of general significance to protein structure due to both its strength and its frequent occurrence. (C) 1999 Elsevier Science B.V. All rights reserved.