Backbone Importance for Protein-Protein Binding.

Although a number of studies have focused on the physical and chemical properties of protein-protein interfaces of complexes to determine their unique features, the importance of the backbone hydrogen bonds to protein-protein binding has been neglected due to the difficulty of quantitatively measuring their contribution to the free binding energy. In this study we are presenting a computational approach that allows the estimation of the contribution to the free binding energy of the CO and NH groups of the backbone of various proteic complexes. A correlation between the quantitative calculated free binding energy contribution of the CO and NH backbone groups of the interfacial residues and the qualitative values expected for this kind of interaction was achieved. The contribution of the backbone to the ΔΔGbinding is significant. The average ΔΔGbinding contribution of the intermolecular hydrogen bonds of the backbone is 1.77 kcal/mol, which is very similar to the average contribution of the different side chains to the ΔΔGbinding, with a value of 1.75 kcal/mol. Therefore, the application of this computational approach as well as an alanine scanning mutagenesis study is essential to a more detailed comprehensive knowledge of proteic complex formation.

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