In silico analysis of pharmacophore modeling for binding Inhibition of VEGF-A and NRP-1 B1 domain

This research explores the inhibition of Vascular endothelial growth factor A (VEGF-A) binding with Neuropilin-1 (NRP-1) B1 domain through pharmacophore modelling of Bevacizumab for its interaction with VEGF-A. The objective of this research was fulfilled with the potential allosteric or secondary binding sites available upon protein-protein docking of VEGF-A and modified bevacizumab in the prevention of angiogenesis. Several 3D conformations of protein structures were obtained and analyzed through visualization alongside pharmacopore modelling by the deletion of the Fc region of the Bevacizumab complex. Upon protein-protein docking, the study found no alteration of binding affinity upon VEGF-A and modified Bevacizumab complex binding in comparison with unmodified Bevacizumab. Therefore, it can be concluded that the Fc region deletion does not affect the binding affinity. However, this is difficult to affirm since the Bevacizumab complex utilized was modified beforehand in the database. Therefore, it is suggested to obtain the Bevacizumab molecule without previous alteration to explore both primary and secondary binding sites. Meanwhile, for the continuation of the current study, it is recommended to test the current stability of VEGF-A and the designed pharmacophore conformation through molecular dynamics simulation or conduct modifications to increase the binding affinity.