Molecular mechanisms of protein-protein recognition: whether the surface placed charged residues determine the recognition process?

We studied the structure and composition of contact areas in 812 different kind dimeric protein-protein complexes from Brookhaven data base (PDB ) in order to reveal their pecularities with regard to protein-protein recognition. We have found, that the large portion of complexes (approximately 70%) have oppositely charged residues in the contact areas (interfaces) on the subunits surfaces, which form electrostatic contacts - R:E, R:D, K:E, K:D, H:E, H:D. These results are consistent with the current view that high rate complex formation may be driven by the long-range electrostatic interaction between charged AA residues of subunits surfaces. However, there are many complexes among the studied ones (approximately 30%), which have no electrostatic contacts at all in their contact area. Thus a question arises: what forces account for high complex formation rates (i.e. for the distant orienting of subunits before encounter) by forming complexes where the surface contact areas lack electrostatic contacts? We believe that the long-range orienting electrostatic interaction of subunits may account for all cases of efficient complex formation if one drops the traditional view that protein subunits interact mainly through their surfaces. We suggest that the distant orienting being due to the electrostatic interaction between the whole aggregates of partial electric charges of atoms of each complex subunits. Our preliminary model calculations (unpublished) made for ribonuclease dimer (does not have electrostatic contacts) conform this suggestion.