Piperidine-based natural products targeting Type IV pili antivirulence: A computational approach

Ozcan A., Keskin O., Sariyar Akbulut B., Özbek Sarica P.

JOURNAL OF MOLECULAR GRAPHICS & MODELLING, cilt.119, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 119
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.jmgm.2022.108382
  • Dergi Adı: JOURNAL OF MOLECULAR GRAPHICS & MODELLING
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, Computer & Applied Sciences, EMBASE, INSPEC, MEDLINE
  • Anahtar Kelimeler: Antivirulence, Drug discovery, Molecular docking, Molecular dynamics simulations, Natural product, PilB, PilF, Piperidine, Type IV pili, Virtual library screening, PSEUDOMONAS-AERUGINOSA, PROTEIN, DOCKING, TOOL
  • Marmara Üniversitesi Adresli: Evet

Özet

Type IV (T4) pilus is among the virulence factors with a key role in serious bacterial diseases. Specifically, in Neisseria meningitidis and Pseudomonas aeruginosa, it determines pathogenicity and causes infection. Here, a computational approach has been pursued to find piperidine-based inhibitor molecules against the elongation ATPase of T4 pili in these two selected pathogens. Using the modeled structures of the PilF and PilB ATPases of N. meningitidis and P. aeruginosa, virtual library screening via molecular docking has returned inhibitor molecule candidates. The dynamics of the best three binders have further been investigated in detail via molecular dy-namic simulations. Among these, ligands with COCONUT IDs CNP0030078 and CNP0051517 were found to have higher potential in the inhibition of ATPases based on molecular dynamic simulation analysis and biological activity information. The obtained results will guide future efforts in antivirulence drug development against T4 pili of N. meningitidis and P. aeruginosa.