Inhibition of SARS-CoV 3CL protease by flavonoids

Jo, Seri; Kim, Suwon; Shin, Dong Hae; Kim, Mi-Sun

All the docking and scoring calculation were performed using the Schr€ odinger software suite (Maestro, version 11.8.012). The compounds were extracted from the PubChem database in the SDF format and were combined in one file. The file was then imported into Maestro and prepared for docking using LigPrep. The atomic coordinates of the crystal structure of SARS-CoV 3CLpro (4WY3) were retrieved from the Protein Data Bank and prepared by removing all solvent and adding hydrogens and minimal minimisation in the presence of bound ligand using Protein Preparation Wizard. Ioniser was used to generate an ionised state of all compounds at the target pH 7 ± 2. This prepared low-energy conformers of the ligand were taken as the input for an inducedfit docking. The induced-fit docking protocol 21 was run from the graphical user interface accessible within Maestro 11.8.012. Receptor sampling and refinement were performed on residues within 5 Å of each ligand for each of the ligand-protein complexes. With Prime 22 , a side-chain sampling and prediction module, as well as the backbone of the target protein, were energy minimised. A total of induced-fit receptor conformations were generated for each of the ligands. Re-docking was performed with the test ligands into their respective structures that are within 30 kcal/mol of their lowest energy structure. Finally, the ligand poses were scored using a combination of Prime and GlideScore scoring functions 23 .