Details

Autor(en) / Beteiligte

• Le, M.-T.
• Mai, T.T.
• Huynh, P.N.H.
• Tran, T.-D.
• Thai, K.-M.
• Nguyen, Q.-T.

Titel

Structure-based discovery of interleukin-33 inhibitors: a pharmacophore modelling, molecular docking, and molecular dynamics simulation approach

Ist Teil von

• SAR and QSAR in environmental research, 2020-12, Vol.31 (12), p.883-904

Ort / Verlag

England: Taylor & Francis

Erscheinungsjahr

2020

Quelle

Taylor & Francis

Beschreibungen/Notizen

• Interleukin (IL)-33 is a new cytokine of the IL-1 family that is related to several inflammatory and autoimmune diseases. IL-33 binds to its ST2 receptor and leads to biological responses thereof. Currently, no drugs have been approved for the treatment of IL-33 related diseases. The aim of this study was to search for small molecules that inhibit the protein-protein interaction between IL-33 and ST2. A virtual screening was first performed to identify potential molecules that can bind IL-33. By analysing the interactions between key residues in the complex of IL-33/ST2, two pharmacophore hypotheses were then generated based on the 'mimicry' and 'pair-rule' principles. From a database of 62,074 compounds, 60 molecules satisfying the pharmacophore models were identified and docked to IL-33. Among 35 compounds successfully docked into the protein, 9 potential ligands in complex with IL-33 were selected for further analysis by molecular dynamics simulations. Based on the stability of the complexes and the interactions of each ligand with the key residues of IL-33, two compounds DB00158 and DB00642 were identified as the most potential inhibitors that can be further investigated as promising novel IL-33 inhibitory drugs.