3.4 Analysis of the PPI together with IFIE
Although electrostatic interaction is an essential component of the molecular interaction, non-electrostatic interaction, i.e., dispersion interaction or van der Waals interaction, is equally important. For fairly understanding of PPI, therefore, non-electrostatic interaction should be considered. As mentioned above, FMO calculations provide the IFIE, that is known to be useful for analyzing the molecular interaction, including the non-electrostatic interaction.
In Figure 3, the RI-MP2 correlation contributions to the interaction energy (i.e., the non-electrostatic interaction energy) are given for amino acid residues in PD-1 and PD-L1 located at the PPI interface. These values were obtained by simply summing up the RI-MP2 correlation energies of the IFIE. The location of these amino acid residues is also given in Figure 3, together with amplitude of the correlation contributions represented by the depth of color. By this analysis, we can understand which residues at the PPI interface are importantly undertaken the non-electrostatic interaction with the other protein. For example, Q75 and I134 of PD-1 have a large non-electrostatic interaction with PD-L1, and Y123 of PD-L1 has an especially large non-electrostatic interaction with the PD-l.
As shown here, information about the non-electrostatic interaction of PPI can be obtained by analysis using the electron correlation contribution of the IFIE. Thus, the combination of the visualization method for electrostatic complementarity and IFIE analysis is one of potential choices to provide physicochemical insight into a PPI.