Teach-Discover-Treat 2
Stop DHODH, Stop Plasmodium, Stop Malaria
Build off the results of last year's Teach-Discover-Treat competition and develop a high-quality pharmacophore model for inhibitors of Plasmodium dihydroorotate dehydrogenase. Inhibitors of this enzyme in the Plasmodium parasite provide an alternative mechanism for the treatment of malaria, a disease that is evolving resistance to existing treatments.

Goal

Develop a pharmacophore model and scoring function for DHODH inhibitors that is useful for virtual screening and pose prediction.

Step 1

Identify key interactions. Click on any of the six DHODH inhibitor structures below to launch a pharmacophore editor session. Although only a single structure may be used as the basis of an editing session, you will want to analyze all six structures to identify the common interactions.

Step 2

Create a pharmacophore model. Choose pharmacophore features and set their properties, such as the search radius or hydrogen bond direction, to specify a pharmacophore query.

Step 3

Evaluate the pharmacophore model. Submit your phamacophore query to search a library of the 167 compounds that were screened as a result of last year's exercise. 44 of these compounds show some inhibition of DHODH at 10μM. Analyze the results of your pharmacophore search to determine how well your model identifies active compounds.

Step 4

Iteratively refine model. Repeat steps 2 and 3 until the model demonstrates a reasonable enrichment of actives compared to inactives. When you are happy with the results, submit your results for evaluation.

Leaderboard
Name F1 TP FP