Discovery of natural agents against Staphylococcus aureus based on EIIC by protein modeling, virtual screening and molecular dynamics

• Published in: Food science & technology 2024-04, Vol.198, p.115914, Article 115914
• Main Authors: Chen, Zhiyuan, Li, Miao, Guo, Yujia, Li, Jianqiang, Wei, Chi, Han, Jiaying, Liu, Chunhong, Bai, Jingwen, Yang, Yu
• Format: Article
• Language: English
• Subjects: alanine; carbohydrate metabolism; cell growth; curcumin; EIIC; enzymes; hydrogen; hydrogen bonding; mechanics; Molecular dynamics; Staphylococcus aureus; Steered molecular dynamics; surface area; van der Waals forces; Virtual screening
• ISSN: 0023-6438; 1096-1127
• DOI: 10.1016/j.lwt.2024.115914

In this study, a reasonable 3D structure of enzyme IIC (EIIC) was established using ab initio methods. Curcumin, baicalein and phloretin were screened out from 127,695 natural products based on EIIC protein in Staphylococcus aureus (S. aureus) by using the virtual screening technology. The antibacterial assays results confirmed that these three compounds could inhibit S. aureus cell growth. The results of molecular docking, molecular dynamics and molecular mechanics/generalized born surface area calculation indicated that curcumin, baicalein and phloretin mainly bound to Glu275, His231, and Phe359 of EIIC through hydrogen bonds and van der Waals forces to obstruct the transport of glucose-based carbohydrates, and thereby inhibited the carbohydrate metabolism of S. aureus. The steered molecular dynamics analysis revealed the existence of transfer channel in EIIC and illustrated that curcumin, baicalein and phloretin could dissociate from EIIC when pulling force on them. Furthermore, alanine scanning and hydrogen bond occupancy analyses found that Glu275 played an important role in stabilizing EIIC-baicalein/curcumin/phloretin complexes, and 275Glu@OE1 was a stable hydrogen bond acceptor. Therefore, Glu275 may be a hot spot residue that can maintain the stable binding of agents to EIIC, which may be a direction for the development of new drugs against S. aureus. •Curcumin, baicalein and phloretin were screened out by virtual screening technology.•The compounds can bind to EIIC to hinder sugar intake inhibiting the bacteria growth.•H-bonds and van der Waals forces had contributions to the EIIC-ligand complexes.•When pulling force on these three compounds, they could dissociate from EIIC.