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ÁLVARO CORTÉS CABRERA Y CRISTINA RUEDA PÉREZ AN. R. ACAD. NAC. FARM.

precision enhancements taking all possible orientations of ligands in
the binding pocket into account (17), at the cost of reducing the time
of the molecular dynamic simulations and obtaining less confidence
in the stability of complexes. Thus, in this work, we chose improved
security in the stability of complexes to an increase of conformations
to be considered while maintaining computational costs affordable.

Figure 4. Correlation between calculated binding energy and EC150 for the test set.

3.3. Binding modes and molecular structure considerations

Evaluated flavonoids have a high shape similarity with natural
agonist of GR. Indeed, in almost all cases a good overlap between
cortisol and the test set molecules can be observed. In order to extract
the most relevant structural features of the ligands, the presence of
hydrogen bonds, the shape and the calculated binding energy were
considered as the principal components when reviewing its capacity
as agonists.

Analyzing the test set, two key factors can be identified: number
and disposition of OH groups. Figure 5 shows the dependence
between the number of OH groups and the energy of binding. In

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