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.