CH⋯O hydrogen bonds at protein-protein interfaces

Abstract

For the first time, a statistical potential has been developed to quantitatively describe the CH⋯O hydrogen bonding interaction at the protein-protein interface. The calculated energies of the CH⋯O pair interaction show a favorable valley at ∼3.3 Å, exhibiting a feature typical of an H-bond and similar to the ab initio quantum calculation result (Scheiner, S., Kar, T., and Gu, Y. (2001) J. Biol. Chem. 276, 9832-9837). The potentials have been applied to a set of 469 protein-protein complexes to calculate the contribution of different types of interactions to each protein complex: the average energy contribution of a conventional H-bond is ∼30%; that of a CH⋯O H-bond is 17%; and that of a hydrophobic interaction is 50%. In some protein-protein complexes, the contribution of the CH⋯O H-bond can reach as high as ∼40 50%, indicating the importance of the CH⋯O H-bond at the protein interface. At the interfaces of these complexes, CαH⋯O H-bonds frequently occur between adjacent strands in both parallel and antiparallel orientations, having the obvious structural motif of bifurcated H-bonds. Our study suggests that the weak CH⋯O H-bond makes an important contribution to the association and stability of protein complexes and needs more attention in protein-protein interaction studies.