Table 1.
Summary of the methods used by participating groups.
| Group | Modeling of Sirtuin 1 structure | Ligand preparation | Processing method of compound library | |||
|---|---|---|---|---|---|---|
| 3D structure modeling/prediction methods/tools | PDB ID used | Filter class | Actives | Decoys | ||
| 1 | — | 4KXQ11 | OMEGA61 | LB→SB | Cambinol, HR73, salermide, sirtinol, suramin, and tenovin | |
| 2 | HM (FAMS)21 | 4BN520 | Open babel62 | LB→SB | Cocrystalized ligands in PDB and ChEMBL (IC50 < 1 μM) | — |
| 3 | — | — | PaDEL-Descriptor23 | LB | MUBD-HDACs63 | |
| 4 | — | 4KXQ | CORINA64 | Hybrid (LB&SB) | PubChem (CID703333, CID71459392) | — |
| 5 | — | 4ZZJ65 | Open babel. Dock27 | Hybrid (LB&SB) | Known Sirtuin inhibitors | — |
| 6 | — | — | RDKit66 | LB | ChEMBL (CHEMBL4506, CHEMBL4462, CHEMBL4461), PubChem (AID 652115), BindingDB (Target = NAD-Dependent Deacetylase Sirtuin 1) | |
| 7 | 4IG9,11 4IF6, 4ZZI,65 4I5I,33 4ZZJ | Ligprep67 | Hybrid (LB&SB) | Cocrystalized ligands | ||
| 8 | MD (myPresto, cosgene37) | 4ZZI | myPresto (AM1, AM1BCC) | Hybrid (LB → SB) | Selisistat (EX-527), Compound 2835 | — |
| 9 | HM and minimization (SWISS model, Foldit) | 4ZZI | Open babel, Discovery Studio visualizer | SB | ||
| 10 | HM (Prime)41,42 | 4ZZI (selected from 4I5I, 4IF6, 4IG9, 4KXQ, 4ZZI, 4ZZJ, 5BTR68) | LigPrep | Hybrid (LB&SB) | ChEMBL (IC50 < 20 μM) | ChEMBL (IC50 > 100 μM) |
| 11 | myPresto (tplgeneX)37,38 | 4I5I | myPresto (create3D) | SB | EX-527 analogue33 | DUD-E8 |
| 12 | — | — | RDKit | LB | BindingDB | ZINC47 |
| 13 | MD | 4I5I | OMEGA | Hybrid (LB, SB&visual inspection) | Sun et al.49 | — |
| 14 | — | 4ZZI | LigandBOX52 | Hybrid (LB & SB) | 8 compounds including Splitomicin, Cambinol, Salerminde | — |
| 15 | — | 4I5I | OMEGA | Hybrid (LB&SB) | Cocrystalized ligands in PDB (4I5I, 4ZZI, 4IF6) | — |
| 16 | 4ZZI | Hybrid (LB → SB) | ||||
Software names are given in italic.
PDB = Protein Data Bank; LB = ligand-based; SB = structure-based; HM = homology modeling; MD = molecular dynamics simulation.