The number of compounds found to demonstrate inhibition at 10μM overall and with respect to the two different methods of ranking compounds.

<p>The number of compounds found to demonstrate inhibition at 10μM overall and with respect to the two different methods of ranking compounds.</p

Query results for top four- and five-feature pharmacophore models.

<p>Query results for top four- and five-feature pharmacophore models.</p

The distribution of tested and active compounds within the submitted (a) Vina ranked and (b) custom ranked compounds.

<p>For each ranking 1000 compounds were submitted from which the TDT organizers sampled a total of 167 compounds for testing. Within the Vina ranking, better scoring compounds are more likely to be active. No such enrichment is observed for the custom ranking.</p

Chemical structure of DHODH inhibitor 5-methyl-7-(naphthalene-2-yl-amino)-1H-[1,2,4]triazolo[1,5-a]pyrimidine-3,8-diium.

<p>The six pharmacophore features used to define the sparse model search space are labeled. Green labels refer to hydrophobic groups, blue labels refer to hydrogen bond features.</p

The ZINCPharmer based interactive pharmacophore modelling interface used by the students to competitively develop an informative pharmacophore model.

<p>The ZINCPharmer based interactive pharmacophore modelling interface used by the students to competitively develop an informative pharmacophore model.</p

Pose prediction of compound 6.

<p>Receptor structure and binding site residues of 3I65 are shown in blue. Compound 6 is shown in magenta sticks. (a) Compound 6 aligned to the pharmacophore of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134697#pone.0134697.g001" target="_blank">Fig 1</a>. The compound makes a hydrogen bond with HIS-185. (b) After minimization, the pose has twisted so that the hydrogen bond to HIS-185 is broken. (c) When the pharmacophore aligned posed is minimized with a flexible ARG-265, which sterically clashes with the initial pose, a less dramatic movement is observed and the hydrogen bond to HIS-185 is maintained.</p

A pharmacophore derived by a student from a structure of DHODH bound to an inhibitor (PDB 3I65).

<p>The pharmacophore consists of hydrophobic features (green spheres) and a hydrogen donor feature (white sphere). This pharmacophore was used as part of a virtual screen for novel inhibitors.</p

Pose prediction results.

<p>The crystal structure of compound 6 (pink sticks) bound to its receptor (silver) is compared to the predicted poses. Pose alignments were obtained by aligning the crystal receptor with 3I65 using PyMOL [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134697#pone.0134697.ref022" target="_blank">22</a>]. (a) The pharmacophore-aligned pose has a heavy-atom RMSD to the crystal pose of 1.77Å while (b) the pose minimized with a flexible ARG-265 has an RMSD of 1.18Å.</p