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

ligand have 3 OH groups. To correct the underestimation of the
electrostatic contribution in the molecule with less than 2 OH groups,
ß = 0.52 was chosen and to correct the overestimation of the same
contribution in the case of more than 4 OH, ß = 0.48 was selected.

After best coefficients were chosen, we used them to calculate the
binding energy of the test set, checking obtained values with expe-
rimental values of activity in an in vitro gene assay (4) expressed as
EC150 or the concentration of substance to produce 150% stimula-
tion of luciferase (GR induced expression) activity.

Table 3. Training set energy values.

Compound Log Kd ?Gexp (KJ/mol) ?Gcalc (KJ/mol)

Dexamethasone 8.47a –48.3 –48.38
Betamethasone 8.45a –48.75 –47.56
Cortisol 8.15b –46.5 –48.96

(a) Values from EMEA (14). (b) Values from Eliard et al. (15).

As can be seen in Table 4, higher electrostatic contributions are
found when more than 2 OH groups are present in the molecule.
Indeed, this effect is due to an overestimation of the force field of
the electrostatic interactions because the polarization effects are not

Figure 3. Training set regression test of calculated and experimental binding energies.

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