eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2025-03-31 18 1 823 834 10.13005/bpj/3132 64891 article Hasanain Abdulhameed Odhar 1 Zanan Abdulhameed Odhar 2 Mustafa Raed Muhi 3 Department of pharmacy, Al-Zahrawi University College, Karbala, Iraq Department of gynecology, Al Mahmoudiya General Hospital, Baghdad, Iraq Department of general surgery, Al Mahmoudiya General Hospital, Baghdad, Iraq The methicillin-resistant Staphylococcus aureus (MRSA) is considered a public health threat that can increase both treatment duration and cost. Currently, the MRSA strain has developed resistance to many penicillins and cephalosporins due to the expression of insensitive penicillin-binding protein 2a (PBP2a). This transpeptidase variant, PBP2a, has a low binding affinity toward the β-lactam ring. As such, the active site of the PBP2a enzyme is now regarded as a potential molecular target for developing new anti-MRSA therapeutics. Many of the available antibiotics were developed from microbial sources but the herbal sources are still to be explored. Therefore, the aim of this in silico study is to virtually screen a library of Traditional Chinese Medicine (TCM) compounds against the active site of PBP2a to identify possible anti-MRSA phytomedicines. For this purpose, both molecular docking and dynamics simulation were employed in this study. Moreover, the agar well diffusion method was used to assess the in vitro antimicrobial activity of final hit compounds against MRSA cultured colonies. The results of the molecular dynamics (MD) study indicate that both sciadopitysin and plantamajoside can maintain a close proximity to the PBP2a active site during 50 nanoseconds simulation. Additionally, the most preferred molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) binding energy was reported to be -24.09 Kcal/ mol for sciadopitysin. While docking study results point to the possible hydrogen bond interaction of sciadopitysin and plantamajoside with Serine 403 active site residue. Further, the agar well diffusion study refers to the fact that both sciadopitysin and plantamajoside are effective in inhibiting the growth of MRSA culture with a measured zone of inhibition: 12.5 ± 0.7 and 9.0 ± 1.4 mm respectively. In conclusion, it is predicted that the phenolic compounds sciadopitysin and plantamajoside from the TCM library are potential inhibitors of the MRSA PBP2a enzyme. https://biomedpharmajournal.org/vol18no1/screening-of-traditional-chinese-medicine-library-against-penicillin-binding-protein-2a-for-methicillin-resistant-staphylococcus-aureus-by-molecular-docking-dynamics-simulation-and-in-vitro-antimicro/ Antimicrobial Activity Docking Dynamics Simulation Methicillin-resistant Staphylococcus aureus Penicillin-binding protein 2a Phytochemical compounds