A novel method for visualizing the electrostatic complementarity of
protein-protein interaction based on fragment molecular orbital method
Abstract
Here, the development of a method for visualizing the electrostatic
complementarity of protein-protein interactions (PPIs) using fully
quantum mechanical electron density (EDN) and electrostatic potential
(ESP) is described. For this method, the partial EDN (pEDN) and partial
ESP (pESP) of each protein were newly defined based on equations used
for the fragment molecular orbital method. To demonstrate the efficacy
of the method, calculations were performed for the complex of programmed
cell death-1 (PD-1) and its ligand (PD-L1). The results showed that the
interface between PD-1 and PD-L1 was appropriately determined by the
pEDN, and that the electrostatic complementarity of the PPI was clearly
represented by visualizing the pESP. Further analysis of the pESP
revealed that additional electrostatic complementarity induced by charge
transfer or polarization due to complex formation was non-negligible
and, therefore, considered important for binding between the proteins.
These findings suggest the efficacy of this method for chemical and
biological studies.