Theoretical estimation of contribution of the electrostatic interactions to pre-orientation of ribonuclease subunits in process of complex formation was carried out. The subunit was considered as a multipole consisting of partial charges of all atoms of the molecule. The object of investigation was a system of two subunits with their centers of gravity fixed at some distance in vacuum. It was proposed that each subunit independently could rotate freely around its fixed center of gravity. The relative orientation states of the subunits in such system were searched at which the system has electrostatic energy minima (equilibrium states). In first approximation the equilibrium states were found using especially designed approximate method for electrostatic interaction energy calculation, which permitted to calculate and compare the energies of the system in 245 (~ 8 106) states with different mutual orientation of subunits. The angular coordinates of the found equilibrium states were further specified by calculation with gradient sliding method. Angular coordinates of the equilibrium states and the shapes of energy surface cuts along each coordinate angle were calculated also for the intersubunits distances diminished down to 50 Å. The dispersions of the angular coordinates of equilibrium states caused by heat movement (at T=300º) and their changes with shortening the distance between centers of gravity of subunits were estimated. Mutual orientation of subunits in the equilibrium states of the system under consideration was found to be similar to their mutual orientations in complex. Also it was found that relaxation time of the system, caused by electrostatic interaction of subunits, after removing the system from an equilibrium state, is much less in vacuum than the mean time between their Brownian collisions at room temperature. It follows from these results that in the case of ribonuclease in vacuum the electrostatic interactions of its subunits must be strong enough to realize the effictive pre-orientation of subunits during their Brownian approach from distances of the order 100 Å. Preliminary consideration taking into account the effect of surrounding water molecules on the electrostatic interactions of ribonuclease subunits showed that weakening of the interaction must be much less than in the case when one uses in its calculation the macroscopic dielectric permeability value equal to 80. So the results obtained for vacuum seem to be true for water solution also.
J. Biomol. Structure & Dynamics, 2004, 22 (1), 111-118.

A software package was designed and used in a detailed study of the contact regions (interfaces) of a large number of protein-protein complexes using the PDB data. It appeared that for about 75% of the complexes the amino acid composition of the subunit surface in the contact region is not essential. Thus one may suggest that, along with the amino acid residues at the interface, the residues in the interior of the globules substantially contribute to protein-protein recognition. Such interactions between quite remote residues are most probably of electrical nature, and are involved in recognition by contributing to the overall electric field created by the protein molecule; the configuration of this field is perhaps the definitive factor of recognition. The overall field of the protein molecule is additively built of the fields created by each constituent residue, and it can be calculated as a sum of the fields created by the protein multipole (aggregate of 'partial' electric charges assigned to every atom of the protein molecule). Preliminary calculations of the remote electrostatic interaction have been performed for ribonuclease subunits in vacuum. The results are indicative of a real possibility that the electric field created by the protein multipole can strongly influence the mutual orientation of molecules before Brownian collisions.

A package of programs for the examination of areas of subunit contacts (interface) in protein-protein (PP) complexes has been created and used for a detailed study of amino acid (AA) composition and interface structure in a large number of PP complexes from Brookhaven database (PBD). It appeared that in about 75% of the complexes, the AA composition of the subunit surface is not important. This suggests that, along with the surface AA composition, interactions between AA from the inner parts of protein globules may play a significant role in PP recognition. Such interactions between relatively distant AA residues can only be of electrostatic nature and contribute to the total electric field of the protein molecule. The configuration of the electric field itself appears to determine the PP recognition. The total electric field created by protein molecules can be calculated as a result of superimposition of the fields created by the protein multipole (i.e. by the totality of partial electric charges assigned to each atom of the molecule). We performed preliminary calculations for the distant electrostatic interaction of ribonuclease subunits in a vacuum. The results reveal that the effect of the electric fields of the protein multipole is strong enough to orient protein molecules prior to their Brown collision.