A data mining and ab initio study of the interaction between the aromatic and backbone amide groups in proteins

Interactions between aromatic groups and backbone amide groups in protein e nvironments are characterized both through data mining analyses of X-ray pr otein structures and through ab initio molecular orbital calculations on a model complex. The data mining analyses of 1029 X-ray protein structures el ucidate the configurational characteristics of the interaction as well as t he positions of the interacting moieties involved. On a statistical average , more than seven such interactions occur in a typical protein structure. T he configurations of these interactions are restricted with the face-to-fac e orientation as the preferred arrangement. The interaction occurs mainly w ithin a single peptide chain. Both alpha-helix and beta-strand secondary st ructures provide an almost equal number of backbone amides to participate w ithin this interaction. The interaction energy was evaluated with the super molecular ab initio method at the MP2 level. It is shown that aromatic-amid e(backbone) interactions identified in proteins can achieve a stabilization energy of 3.3 kcal/mol. The interaction involves the entirety of the backb one amide rather than only its amine portion. This study concludes that the interaction between aromatic and backbone amide groups is of general signi ficance to protein structure due to its strength and common occurrence. (C) 2000 John Wiley & Sons, Inc.