Molecular Dynamics Simulation Studies of Beta-Glucogallin and Dihydro Dehydro Coniferyl Alcohol from Syzygium cumini for its Antimicrobial Activity on Staphylococcus aureus.

ABSTRACT

With the escalating threat of antimicrobial resistance (AMR), discovering novel therapeutic agents against resistant pathogens like Staphylococcus aureus is crucial. This study explores phytochemicals from Syzygium cumini for their potential efficacy against AMR S. aureus infections, elucidating their mechanisms through in silico methods. We investigated 83 compounds from S. cumini, sourced from PubMed, using rigorous docking analysis against the ATP binding domain AgrC of S. aureus with AMdock with Autodock Vina v1.5.2. Drug-likeness predictions were assessed using SwissADME v2023 and Pass online v2.0. Molecular dynamics (MD) simulations identified promising compounds, focusing on stability and interaction dynamics. Beta-Glucogallin (BEG) and Dihydro Dehydro Coniferyl alcohol (DIH) emerged as significant hits. MD simulations with GROMACS v2020.6 revealed stable BEG and DIH complexes with AgrC, forming six hydrogen bonds with six key amino acids (Arg-303, Asp-338, Glu-342, Glu-384, Lys-389, Gly-396), indicating strong and stable bonding. The binding affinities for DIH and BEG are -73.474 ± 11.104 kJ/mol and -6.319 ± 18.823 kJ/mol with 4BXI, respectively. Our findings highlight BEG and DIH as promising candidates against AMR S. aureus infections, showing favourable binding affinities and stable interactions with AgrC. This study underscores the importance of natural products in combating AMR and demonstrates the utility of computational methodologies in drug discovery. Further experimental validation is warranted to fully exploit these phytochemicals' therapeutic potential.