Integrated Experimental and Computational Study Explain Cysticidal Effects by Suppression of Novel Acanthamoeba Cyst Protein, Poly(ADP-Ribose) Glycohydrolase : New Molecular Target for combating Acanthamoeba infections

The present research aims to evaluate the Acanthamoeba cyst’s membrane integrity by targeting the breakdown of β-glucan using the β-glucanase enzyme, which combines with chlorhexidine. Then, the proteins involved in downregulating the protein expression were identified. The protein-protein complex interaction generated using PDBSum, including the schematic diagram and the residue across the interface interaction diagram, proved the residues of PARG interconnected through various interactions with 23 β-glucanase residues. Overall, there are 152 interactions, which consist of 4 salt bridges, 14 hydrogen bonds, and 134 non-bonded contacts, which include the Van der Waal bonds. The result further solidifies the inference of the stability of PARG-β-glucanase enzyme. In-silico experiments were done to expand upon the interactions involved in the combined drug therapy on Acanthamoeba cyst, which includes model development, model evaluation, and molecular docking of each therapeutic agent with Poly (ADP Ribose) Glycohydrolase (PARG) of Acanthamoeba castellanii (AcPARG). Molecular docking between AcPARG and chlorhexidine produces a complex with a binding energy of −9.1 Kcal/mol, and the HADDOCK protein-protein docking of AcPARG and β-glucanase enzyme predicted the bound compound with a HADDOCK score of -173.6 +/- 9.6. Biocomputational analysis shows that both therapeutic drugs, chlorhexidine and β-glucanase enzyme, form stable complexes and favourable interactions with AcPARG.