Structural-based virtual screening and identification of novel potent antimicrobial compounds against YsxC of Staphylococcus aureus

• Published in: Journal of molecular structure 2022-05, Vol.1255, p.132476, Article 132476
• Main Authors: Kumari, Reena, Rathi, Ravi, Pathak, Seema R, Dalal, Vikram
• Format: Article
• Language: English
• Subjects: MMPBSA; Molecular docking; Molecular Dynamics Simulation; Staphylococcus aureus; YsxC
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.132476

•Molecular modeling and screening of Ribosome biogenesis GTP-binding (YsxC).•Identified molecules were filtered via pharmacokinetic and ADMET properties.•Molecular docking was conducted to evaluate binding affinity and interactions.•Molecular dynamics and MMPBSA confirmed the stability of protein-ligand complexes.•Here, five potent novel molecules against YsxC of S. aureus were reported. Ribosome biogenesis GTP-binding (YsxC) is a GTPase, an essential protein involved in ribosomal assembly and protein synthesis in Staphylococcus aureus. In the current study, we built a 3-dimensional model of YsxC and used it to identify potent molecules against S. aureus. A total set of 5968 antibacterial molecules from asinex database were screened at the active site of YsxC. Molecular docking studies of pharmacokinetic filtered molecules were done to confirm the binding affinities and interactions of screened molecules with YsxC. Based on the molecular docking results, five molecules (BDE 33512592, BDF 33512588, BDE 33512301, BDE 33512449, and BDE 33512649) had higher binding affinity than GTP. All the identified molecules were stabilized via hydrogen and hydrophobic interactions with YsxC. Molecular dynamics analysis confirmed that YsxC-inhibitor(s) complexes were less dynamics and higher stable than YsxC-GTP complex. Molecular Mechanics/Position-Boltzmann Surface Area (MMPBSA) concluded that Arg33, Ser34, Asn35, Val36, Lys38, Ser39, Thr40, Thr54, Ser55, Gln56, Pro58, Lys60, Thr61, Lys145, Asp147, Ser178, and Ile179 of YsxC played an important role in the formation of lower energy YsxC-inhibitor(s) complexes than YsxC-GTP complex. The identified molecules need to be tested in vitro and may be used to design novel compounds against S. aureus. [Display omitted]