Create a library of compounds containing a common scaffold
Retrieve bioactivity data for this library
Compare the activity scores for tested compounds in multiple assays
Interpret the activity scores in light of structural clustering of the tested compounds
Steps
Open the PubChem Sketcher
On the NCBI home page, choose PubChem Compound from the Database
menu, and click Go.
On the left sidebar, click PubChem Structure Search.
Click the Sketch button.
Draw a model of a compound using the Sketcher
In this exercise you will draw the scaffold below and submit it for a substructure search to find the PubChem
Compound records that contain the scaffold. To create the structure you will click on selections in the Control panel
on the left and use them to click and draw your structure in the Drawing window on the right.
Please note the New, Undo and Del
(delete) buttons on the top button row in the Control panel in case you make a mistake and would like to fix the problem without starting over.
Draw the three rings
Click on the cyclohexane icon in the second row of substructures and click in the Drawing window
to create the central ring.
Attach the benzene ring by clicking on the benzene icon in the second row of substructures
and clicking on the bottom atom of the central ring.
Add the furan ring by first selecting the double bond icon and clicking on the upper left atom of the central ring.
Next select the cyclopentane icon (next to cyclohexane) and click on the end of the double bond.
Add substituents
Add the remaining double bonds to the central ring, and then to the cyclopentane ring.
Substitute oxygen, nitrogen and sulfur atoms into the structure by clicking on the atoms in the top row
of the modified periodic table and then sequentially clicking on the appropriate sites.
Click the Done button when finished.
Search the PubChem Compound database with your drawn structure
Click the Advanced radio button to the right of Structure Search at the top of the page.
Set the Search using menu to Substructure.
Set the Result limit to 10,000.
Click the Search button.
Retrieve bioactivity data for the library
When the search is done, choose PubChem Bioactivity Summary from the Display menu.
How many of compounds in the library have been tested in these BioAssays? What is the function of these compounds?
Locate in particular the Rnase assays.
View an SAR analysis of the tested compounds
Check the boxes to the left of the Rnase assays.
Click the Structure Activity tab near the top of the page.
Explore the heatmap. It may be easier to cluster the compounds by activity. To do this, click the Activity Similarity button in the Compound Cluster row.
View the assay data table for selected compounds
Scroll to the region of the heatmap showing the active compounds (red).
Select a region in the heatmap containing active and inactive compounds by clicking first on the upper left and then lower right of the rectangular region you want.
In the resulting menu, click Bioassay Data Table, Selected Compounds and BioAssays.
Which compounds are active? Inactive? Are there any structural features that seem to confer activity?
Analyze the assay data
Click the column title AID_372 Score to sort the table by these scores (unless it's
already sorted this way). What is the most active compound in AID 372?
Find the inactive compounds. How active are these compounds in AID 372?
Sort the table by the Scores in one of the other assays by clicking on a Score column. Where are the active/inactive compounds now in the list?
