Solvation and conformational properties of melatonin: a computational study
The conformational space of melatonin, as defined by dihedral angles representing different orientations of the carboxamido ethyl side chain, was calculated in vacuum and aqueous solution, using the AM1 semiempirical methodology, and the AM1-SM2.2 solvation model, respectively. The effects of conformation and aqueous solvation on several molecular properties typically used as descriptors in structure-activity relationship studies, such as Mulliken charges and the HOMO-LUMO gap, were considered. In the case of the charges on the O(3) and N(4) atoms, the effects of conformation were shown to be larger than those due to structural changes, while the charge on O(16) was greatly affected by structural and very little by conformational changes. Based on the computed values for this charge in analogs with different binding affinities, we suggest that the electrostatic features of the 5-methoxy moiety do not modulate binding affinity. Taken together, our results suggest that conformational and solvation effects should be considered in order to obtain realistic structure-activity relationships of the melatonin system.
solvation conformation melatonin