two sublots,ax[0]andax[1], showing a histogram of the signal
inhibition and a scatter plot of the signal inhibition versus molecu-
lar similarity side by side. (If you are new or unfamiliar with the
matplotlibsyntax, it is recommended to consult the tutorials and
resources listed in section2.5.)
From the histogram (left panel of Fig.7), we can see that most
molecules inhibit the DKPES signal by less than 50% in in vivo
EOG assays. The scatter plot in Fig.7 shows that four out of the five
most active molecules have a high overlay similarity value of 1.5 or
greater. TheTanimotoCombovalue is the sum of the volumetric and
chemical similarity components, where an exact match (two identi-
cal molecules in the same conformation) will result in a maximum
score of 1 for each, summing to a maximum score of 2. While the
top four most active molecules have the highest overlay similarity,
no correlation between overlay similarity and signal inhibition can
be observed across the remaining 52 molecules. This indicates that
more specific determinants of activity are at play, motivating the
pattern analysis of functional groups matching DKPES. Interest-
ingly, the outlier with a very low Tanimoto similarity score and a
moderately high signal inhibition value of 0.62 is a sulfate tail-
containing natural product (ZINC14591952) produced by sea
squirts [29], shown in Fig.8.
From this molecule we can conclude that mimicking the sulfate
group in DKPES alone can block the olfactory response of DKPES
by approximately 60%, likely by competing with interactions of the
similar tail in DKPES with the GPCR ligand binding site.3.2 Chemical and
Functional Groups
This section explains how to visualize the other features in the
dataset: the functional group matches with the DKPES reference
molecule (Fig.2). Using the code in Fig. 9, we will plot the
functional group matching pattern of the top ten most active and
ten least active molecules via two heat maps shown side by side for a
visual comparison (seeNote 6).Fig. 8Sulfate tail compound sodium 6-methylheptyl sulfate (carbon atoms
shown in green; ZINC14591952, average of 62% signal inhibition in EOG
experiments) overlaid with the most similar DKPES conformer (carbon atoms
shown in cyan)318 Sebastian Raschka et al.