ZINC15:Getting started

ZINC15 is a major revision of ZINC that aims to allow you to ask more questions and get answers more easily. ZINC15 is still new (September 2015) and remains a little rough around the edges. Still, we wanted to get it into your hands so that you can start to benefit from it. One important thing: ZINC15 is a work in progress. It will continue to change as we make improvements. We will do our best to keep this documentation current.

If you hate reading and just want to do cool things, try ZINC15:examples and ZINC15:videos. Otherwise, to get started methodically, browse to zinc15.docking.org.

Initial orientation

The welcome page / splash screen contains a navigation bar on the top that allows you to go to the different resources in ZINC15. The ZINC button (left) will bring you back to the welcome page. The four most popular resources are displayed next: Substances, Catalogs and Genes, and Tranches. Clicking on them takes you to them. A comprehensive list of resources is found in the More popup menu. On the right Is an About popup that gives you access to help and other information. Three other sections below offer different ways to get going. Getting started links to articles in this wiki. Explore resources links directly to several interesting starting points such as ATC codes, genes, patterns and rings. Ask Questions lists some interesting questions that ZINC can answer, and the more button in this section leads to further examples. Finally, ZINC 15 news contains recent announcements.

Substances

To search for substances, click on substances in the navigation bar. This takes you to a molecule search page. Here you can simply browse substances (click Browse), explore subsets (Subsets button) or search for a molecule (enter ZINC ID, SMILES, SMARTS, InChI or name into the field below the Draw/Search Structure heading. You search for molecules using the buttons below the drawing window. There is a many molecule search tool on the right side of this page.

Substance subsets

Click on the subsets button to see available substance subsets. (the URL now ends with /substances/subsets). There are purchasability subsets, bioactive and drug subsets, biogenic subsets, reactivity and other subsets. To search for FDA approved drugs, click on fda.

Substance listing page

You are now on the substance listing page (URL ends with /substances/subsets/fda). At the top is a page navigation tool, a Get Total button, a Download tool, the breadcrumbs, filters, resources, and a search tool.

• to search for only FDA molecules that also available for immediate delivery, use the subsets tool (a label icon) to display a popup. The popup shows that fda has already been selected. Now select now.

• to search for which of these drugs hit bacterial targets, click on the relations tool (a chain link icon). In the popup, select organism and then type bacteria. Click the blue link icon to apply your choice. (40 drugs selected).

• To find which bacterial targets paroxetine hits, click on paroxetine (ZINC527386). Scroll down the molecule detail page. You will see NORA, the Quinoline resistance protein NorA.

• To find the paper where this activity was reported, click on the 1 under obervations. (url is now genes/NORA/observations/?zinc_id=ZINC000000527386)

• To go to the paper, click on the PMID (J Med Chem 2011)

• To see all the compounds reported in that paper that are in ZINC (via ChEMBL) click on the DOC ID number. URL is now /docs/58576/.

We hope this helps you get started exploring using ZINC 15.

Downloading SMILES

To download a library in 2D, use the tranche browser by clicking on Tranches in the navigation bar. Across the top of the page the following tools are available:

• Representation selector: 2D or 3D
• Reactivity selector: Anodyne, Clean, Mild, Reactive, Unstable. Default Mild (ZINC12 default)

Please note: curation of patterns is ongoing and will change in the coming months. In particular, the Reactive and Unstable annotations have not yet been properly curated

• Purchasability selector: In Stock, Agent, On Demand, Boutique, Annotated. Default On Demand (ZINC12 default).

Reactivity and purchasability are by default cumulative selectors. To select compounds that are only a the specified level, toggle the exclusive option at the bottom of each popup.

• pH : only applies in 3D
• Charge: only applies in 3D
• Predefined subsets: rapid selection of common subsets. Looks like a 3x3 array.
• Download button, when all other choices have been made. Options are:
  • format: SMILES or txt.
  • method: curl, wget, urls. default is raw URLs.

• To select just "lead like" compounds, use the predefined subsets selector, which looks like a 3x3 array of dots.
• Click on the download tool (top right). Default is mild reactivity (includes aldhydes, michael acceptors and PAINS). Default purchasability is On demand, as it was in ZINC12.
• Click on Download.

Note: This downloads a script which allows you to get the molecules. The script must be run to get the molecules.

We hope this has given you some idea of how to get started with ZINC15. Good luck!