Computational protocol: Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells

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Protocol publication

[…] The three-dimensional structure of wedelolactone was downloaded from ZINC database [], (ZINC ID: ZINC6483512). The output file in Sybyl mol2 format was converted into AutoDock Vina [] compliant pdbqt format by MGLTools []. The crystal structure of yeast 20S proteasome (PDB ID: 5CZ4) was used as a target in molecular docking. All ligands and water molecules were removed from the target molecule. The hydrogen atoms were added to the target by PyMol []. The Gasteiger charges and AutoDock atom types were assigned to targets by MGLTools. The active site of β1 (caspase-like activity), β2 (trypsin-like activity) and β5 (chymotrypsin-like activity) subunits and both inner β rings were selected as target regions for molecular docking performed by AutoDock Vina. The region selected for focused docking was represented by a box of 22.5 Å × 22.5 Å × 22.5 Å centered at the catalytic residue Thr1. The entire protein surface was selected for a blind docking to assess the specificity of wedelolactone towards the enzyme active sites. The region selected for the blind docking was represented by a box with 87.5 Å × 87.5 Å × 87.5 Å dimension centered at the middle of the two inner β rings harboring the active sites. Ten and twenty conformations were produced by AutoDock Vina in the focused and blind docking, respectively. The docked conformations were re-scored by NNScore 2.0 [], which predicts binding affinity of the conformation as an average over 20 distinct neural-networks. […]

Pipeline specifications

Software tools AutoDock Vina, PyMOL, AutoDock
Application Protein interaction analysis
Diseases Breast Neoplasms, Neoplasms, Drug-Related Side Effects and Adverse Reactions
Chemicals Copper, Oxygen