Title:Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5
Volume: 19
Issue: 10
Author(s): Hoora Hashemi, Malihe Hassanzadeh and Massoud Amanlou
Affiliation:
Keywords:
Fragment-based, molecular docking, pharmacophore model, TLR5, virtual screening, molecular dynamics.
Abstract: Aim and objective: Rheumatoid Arthritis (RA) is a progressing
autoimmune inflammatory disease of joint, hallmarked by inflammation, pain and
atrophy of bones. Toll-like receptor 5 (TLR5) is a novel inflammatory mediator in
RA, and TLR5 inhibitors are speculated to have a therapeutic potential for the
treatment of RA.
Material and method: Here we applied fragment pharmacophore-based virtual
screening to identify novel TLR5 ligands.
Results: Among compounds collected from Otava peptidomimetic compounds,
Maybridge fragment and ZINC libraries, 3355 compounds were selected for docking
into the flagellin-binding site of TLR5. 16 compounds with the required interaction, critical amino acid
residues and the binding free energies <-7 kcal/mol were identified as potential TLR5 inhibitors, one of
which was followed up by molecular dynamics simulation.
Conclusion: These compounds open a possibility to discover novel TLR5 inhibitors for the treatment
of RA.
