Molecular Docking and Molecular Dynamics Simulation Insight of Amidase_2 Endolysin Domain as an Antifungal Enzyme

The availability of the constrained number of antifungals and the development of resistance against them is of major concern. The common monomers present in bacterial peptidoglycan and fungal chitin layer propose the activity of antibacterials as antifungals. This study involves molecular docking and molecular dynamics simulation applications to evaluate the antifungal activity of bacteriophage endolysin domain amidase_2. The binding free energy of – 6.6 and – 5.6 kcal/mol were calculated for the amidase_2 domain-muramyl dipeptide and chitin complex respectively. The amidase_2 amino acid residues HIS214, GLU282, and HIS324 essential for its catalytic activity were found to form hydrogen bonds with chitin. The root mean square deviation results signified the binding of ligands to the catalytic pocket of amidase_2 with an increased value. The root-mean-square fluctuation, radius of gyration, free energy landscapes, and principal component analyses displayed stabilization of the amidase_2-chitin complex. The interaction analysis displayed amidase_2 domain residues TRP263, ALA238, and THR269 in hydrophobic interaction with chitin; whereas HIS324 was found to form the salt bridge. The amidase_2 amino acid residues HIS214, ARG236, and HIS324 formed salt bridges with muramyl dipeptide. The residues GLY240, ILE241, and HIS324 favored the binding of amidase_2 domain to both muramyl dipeptide and chitin. This study indicates the effective binding of identical amidase_2 amino acid residues with peptidoglycan and fungal cell wall components in a stabilized low-energy environment. With the support of computational simulations, amidase_2 can be explored as an antifungal enzyme along with anti-staphylococcal activity by further evaluation through in-vitro and in-vivo analysis.