Table 5.

The average electrostatic (ele) and van der Waals (vdW) nonbonded interactions of curcumin, 6-gingerol, capsaicin, and resveratrol in water (the free state W) as well as in complex with PDE4D (the bound state P) along with the corresponding binding free energies.

Energies	$⟨V_{vdW}^{L-P}⟩$ (kcal/mol)	$⟨V_{vdW}^{L-W}⟩$ (kcal/mol)	$⟨V_{ele}^{L-P}⟩$ (kcal/mol)	$⟨V_{ele}^{L-W}⟩$ (kcal/mol)	$⟨V_{ele}^{L-P}{⟩}_0$ (kcal/mol)	$∆G_{binding}^{L-P}$ ** (kcal/mol)
Curcumin
Production run 1	−53.72	−33.43	−60.10	−40.34	−0.66	−10.83
Production run 2	−52.38	−33.41	−62.07	−40.55	−0.73	−11.24
Production run 3	−52.33	−33.52	−61.04	−39.43	−0.69	−11.22
Production run 4	−52.94	−33.41	−60.43	−40.23	−0.69	−10.85
Average *	−52.84 ± 0.64	−33.44 ± 0.05	−60.66 ± 1.15	−40.14 ± 0.49	−0.69 ± 0.03	−11.03 ± 0.25
6-Gingerol
Production run 1	−49.25	−24.38	−49.89	−43.84	−0.49	−6.97
Production run 2	−50.71	−24.49	−49.37	−43.16	−0.51	−7.27
Production run 3	−49.11	−25.40	−50.58	−44.17	−0.47	−6.85
Production run 4	−48.15	−24.36	−49.98	−43.53	−0.44	−6.85
Average *	−49.56 ± 1.52	−24.66 ± 0.50	−49.96 ± 0.50	−43.67 ± 0.43	−0.48 ± 0.03	−6.99 ± 0.39
Capsaicin
Production run 1	−50.33	−28.20	−38.69	−35.67	−0.38	−5.36
Production run 2	−52.33	−27.72	−37.29	−35.81	−0.35	−5.27
Production run 3	−52.62	−27.74	−37.39	−35.76	−0.36	−5.37
Production run 4	−50.67	−28.30	−38.37	−36.70	−0.38	−4.96
Average *	−51.49 ± 1.15	−27.99 ± 0.31	−37.93 ± 0.70	−35.99 ± 0.48	−0.37 ± 0.02	−5.24 ± 0.35
Resveratrol
Production run 1	−31.64	−16.53	−51.15	−47.18	−0.53	−4.57
Production run 2	−30.18	−16.44	−51.90	−47.04	−0.50	−4.58
Production run 3	−29.80	−16.46	−52.68	−47.61	−0.48	−4.56
Production run 4	−30.58	−16.49	−52.48	−47.59	−0.49	−4.65
Average *	−30.55 ± 0.39	−16.48 ± 0.04	−52.05 ± 0.65	−47.36 ± 0.35	−0.51 ± 0.02	−4.59 ± 0.41

* The average values of all corresponding production runs are presented as mean ± standard deviation. Standard deviations were calculated from corresponding mean contributions obtained in four independent 10 ns production runs of MD simulations. ** Binding free energies were calculated with preoptimized values of α = 0.18 and β = 0.33. The experimental binding free energy of a positive control rolipram equals −9.86 kcal/mol [83].