ZINC: a free tool to discover chemistry for biology

Abstract

ZINC is a free public resource for ligand discovery. The database contains over twenty million commercially available molecules in biologically relevant representations that may be downloaded in popular ready-to-dock formats and subsets. The Web site also enables searches by structure, biological activity, physical property, vendor, catalog number, name, and CAS number. Small custom subsets may be created, edited, shared, docked, downloaded, and conveyed to a vendor for purchase. The database is maintained and curated for a high purchasing success rate and is freely available at zinc.docking.org.

Figure 1

Physical properties of popular standard subsets. Color scheme: lead-like (blue); fragment-like (red); drug-like (green), all-purchasable (purple), everything (cyan). Nine properties: (A) molecular weight (Daltons); (B) calculated LogP; (C) heavy atom count; (D) rotatable bonds; (E) polar surface area (A²); (F) hydrogen-bond donors; (G) hydrogen-bond acceptors; (H) polar desolvation energy (kcal/mol); (I) apolar desolvation energy (kcal/mol).

Figure 2

Physical properties of lead-like subsets. Color scheme: lead-like (blue); clean-leads, containing only benign chemical functionality (red); leads-now, in stock for two week delivery (green). Nine properties: (A) molecular weight (Daltons); (B) calculated LogP; (C) heavy atom count; (D) rotatable bonds; (E) polar surface area (A²); (F) hydrogen-bond donors; (G) hydrogen-bond acceptors; (H) polar desolvation energy (kcal/mol); (I) apolar desolvation energy (kcal/mol).

Figure 3

pH dependent representation of molecules in ZINC illustrated by examples. (A) Protonation of histidine, (B) tautomerization of folate, (C) deprotontation of sulfonamide for metals, and (D) protonation of aniline at low pH.

Figure 4

ZINC combination search page . The drawing panel is to the left, and the SMILES field displays and allows editing of the SMILES of the current molecule. The Redraw button updates the current SMILES in the drawing panel. The similarity level selector may be used to select the Tanimoto cutoff to be used, or substructure. The (+) button adds a new SMILES. The report control bar controls how the results will be filtered and formatted. It contains page size specification, format selector, representations selector, purchasability selector, and a Run Query button. To the right is shown the property selection control bar, including the preset selector (top right) allowing easy selection of popular choices.

Figure 5

ZINC search results as 2D tiles, the default report format. Molecules may be added to the active cart by clicking on them, making them blue. Hovering the mouse over a molecule reveals a popup with additional detail about purchasability, physical properties, and other similar molecules. The report control bar allows additional report formats and changes to purchasability and pH. It contains page number, next page button, page size specification, format selector, representations selector, purchasability selector, Add all to add all molecules to the active cart, and Refresh to apply any changes that are made.