Molecular docking and simulation studies of flavonoid compounds against PBP-2a of methicillin-resistant Staphylococcus aureus

J Biomol Struct Dyn. 2021 Jul 9;1-17. doi: 10.1080/07391102.2021.1944911. Online ahead of print.

Abstract

Methicillin-Resistant Staphylococcus aureus (MRSA), a pathogenic bacterium that causes life-threatening outbreaks such as community-onset and nosocomial infections as emerging 'superbug'. Time and motion study of its virulent property developed resistance against most of the antibiotics such as Vancomycin. Thereby, to curb this problem entails the development of new therapeutic agents. Plant-derived antimicrobial agents have recently piqued people's interest, so in this research, 186 flavonoids compound selected to unmask the best candidates that can act as potent inhibitors against the Penicillin Binding Protein-2a (PBP-2a) of MRSA. Molecular docking performed using PyRx and GOLD suite to determine the binding affinities and interactions between the phytochemicals and the PBP-2a. The selected candidates strongly interact with the different amino acid residues. The 30 ns molecular dynamics (MD) simulations with five top-ranked compounds such as Naringin, Hesperidin, Neohesperidin, Didymin and Icariin validated the docking interactions. These findings are also strongly supported by root-mean-square deviation, root-mean-square fluctuation and the radius of gyration. ADME/T analysis demonstrates that these candidates appear to be safer inhibitors. Our findings point to natural flavonoids as a promising and readily available source of adjuvant antimicrobial therapy against resistant strains in the future.Communicated by Ramaswamy H. Sarma.

Keywords: ADME/T properties; Penicillin Binding Protein-2a; flavonoids compounds; methicillin-resistant staphylococcus aureus; molecular docking; molecular dynamic simulation.