Boerhavia diffusa plant extract can be a new potent therapeutics against mutant nephrin protein responsible for type1 nephrotic syndrome: Insight into hydrate-ligand docking interactions and molecular dynamics simulation study

Nephrotic syndrome type 1 is an inherited condition in which mutation of NPHS1 gene, which encodes nephrin protein, results increase permeability of glomerular capillary wall for macromolecules causes heavy proteinuria, hypoproteinemia, and edema. Nephrotic syndrome patients are resistant to steroid and immunosuppressive treatment. Natural products have traditionally been used to treat a number of chronic diseases. Present study was focused to investigate potency of different phytochemicals found in Boerhavia diffusa (B.diffusa) plant against mutant nephrin protein. The study involves virtual screening of total 66 bioactive compounds from B.diffusa plant against wild type and mutant models of Ig4 domain of nephrin protein through AutoDock raccoon. Based on binding energy and drug-likeness property, seven phytocompounds were screened. Hydrate-ligand docking (addition of explicit waters in ligands) method was used to select potential phytocompounds that could bind to mutant model of Ig4 domain of nephrin protein. For further prediction, molecular dynamics simulations with 100ns trajectory of Ig4 domain of nephrin protein in glycolipid bilayer membrane for systems such as wild, mutant, mutant model complex with boeravinone M and mutant model complex with boeravinone E were thoroughly studied. Hydrate-ligand docking result predicted boeravinone M and boeravinone E have shown better binding performance with mutant model. It causes due to hydration force field that measures entropy and enthalpy for each water molecule separately, allowing for more exact estimations of their contribution to ligand-protein interaction. Boeravinone E shows lowest short-range Lennard-Jones (LJ-SR) interaction energies of-47.78 +/- 12.7 kJ/mol. The results showed reduced compactness and stability nature of mutant model of Ig4 domain of nephrin protein, however, binding with boeravinone E has effectively modulated its stability and function by increasing its compactness. Current study may provide insight into therapeutic development of boeravinone E as a potential inhibitor against NPHS1in near future.

Automated summary

This study investigated the potential of different phytochemicals found in Boerhavia diffusa plant against mutant nephrin protein. Results showed that boeravinone E may act as a potential inhibitor against Nephrotic syndrome type 1 and modulate the stability and function of the mutant nephrin protein.