Publication: Piperidine-based natural products targeting Type IV pili antivirulence: a computational approach
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KU-Authors
KU Authors
Co-Authors
Ozcan, Aslihan
Akbulut, Berna Sariyar
Ozbek, Pemra
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Abstract
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.
Source
Publisher
Elsevier
Subject
Biochemical research Methods, Biochemistry, Molecular biology, Computer science, Crystallography, Mathematical and computational biology
Citation
Has Part
Source
Journal of Molecular Graphics and Modelling
Book Series Title
Edition
DOI
10.1016/j.jmgm.2022.108382