Intermolecular interactions and charge density distribution of endocrine-disrupting molecules (xenoestrogens) with ER alpha: QM/MM perspective

摘要

Xenoestrogens are endocrine-disrupting chemicals which are mimicking the action of estrogens in the active site of estrogen receptor-alpha (ER alpha). Bisphenol A, nonylphenol, and octylphenol are the few endocrine chemicals called xenoestrogens that bind to the estrogen receptor. Several reports outline the mimic action of xenoestrogens in the active site of ER alpha that these molecules bind to ER alpha and has high estrogenic activity as the estrogens does and how they induce the cancer disease. Binding affinity of these molecules to the receptor ER alpha always rely on their conformation and the interaction with the nearby active site amino acids of the receptor and the charge density distribution. The molecular docking, QM/MM-based charge density analysis of bisphenol A (BPA) has been performed, which gives the conformation, charge density distribution, and the electrostatic properties in the presence of active site amino acid residues of ER alpha. The QM/MM charge density analysis of active site form of BPA reveals the nature of their chemical bonding and the strength of interactions with the neighboring residues present in the active site of ER alpha. The electrostatic potential map of BPA in the active site shows the reactive locations in the molecules and the corresponding interactions with ER alpha. The global reactivity descriptors show the reactive nature and the toxicity of the molecule. This study confirms that the BPA molecule binds to the active site amino acids of ER alpha as the estrogen molecule 17 beta-estradiol binds, which leads to the cell proliferation in the breast cancer cells and inhibits apoptosis.