The Structural Bioinformatics analysis of Biophenolic Lignan-Estrogen Receptor interaction.

BACKGROUND

Plant lignans have proven efficacious in blocking estrogen receptors of breast cancer cells. However, available studies have mostly dealt with anti-cancer effects of groups of lignans in certain foods or plants and the effects of specific lignans, especially from a molecular interaction viewpoint, has been rarely addressed in the literature.

OBJECTIVE

We aimed to computationally predict the binding ability and binding strength of pinoresinol, matairesinol, lariciresinol and secoisolariciresinol as potent ligands of estrogen receptor alpha (ER-α), in order to study these lignans as drugs.

METHODS

Blind Docking method was utilized to predict the binding orientation of lignans to their targets by AutoDock 4.2 software. Docking results of lignan-receptor complexes were compared to tamoxifen-receptor complex separately. Hydrophobic interactions and hydrogen bonds between lignans and ER were perused and the binding energy was calculated.

RESULTS

The best binding affinity of tamoxifen, matairesinol, pinoresinol, lariciresinol and secoisolariciresinol were respectively -8.7, -7.5, -6.7, -6.7, -5.8 kcal/mol, and matairesinol showed the minimum binding energy than other studied lignans. Matairesinol showed the most similar interactions with tamoxifen with small molecule-receptor complex in the following residues: Leu:391, Ala:350, Ile:424 and Phe:404.

CONCLUSIONS

Among the studied lignans, matairesinol showed the least binding energy as well as the most similar hydrophobic interactions to tamoxifen suggesting that matairesinol can display more efficacious biological activity to inhibit ER in comparison with pinoresinol, lariciresinol and secoisolariciresinol. Thus, our results introduce matairesinol as a potentially effective anti-ER drug.