4. CONCLUSIONS
In this study, a novel method for visualizing the electrostatic complementarity in a PPI was proposed using the pEDN and pESP, which were introduced by limiting the summation of the FMO equations of the total EDN and ESP. In this method, the PPI interface is defined using the pEDNs of the proteins obtained from the FMO calculation for the complex, followed by visualization of the pESP of the proteins at the PPI interface. To show the potential of this method, the PD-1/PD-L1 complex was selected as an illustrative example. The results successfully demonstrated that the PPI interface was appropriately determined according to the pEDN, and that electrostatic complementarity was clearly represented by visualizing the pESP. Interestingly, additional electrostatic complementarity induced by charge transfer or polarization due to complex formation was explicitly revealed, indicating its important role in PD-1/PD-L1 binding. Notably, such information cannot be obtained without a fully quantum mechanical ESP. Thus, we can conclude that the method proposed in this study is useful for chemical and biological investigations.
A potential application of this method is the design of antibodies, which is recently used as a therapeutic agent because of its high affinity and specificity to the target protein. Especially, the specificity is considered to be strongly related to the electrostatic complementarity between antibody and its target. Consequently, use of the proposed method could increase the efficiency of antibody design and will be the focus of future research.