Investigation of the effect of estrogen receptor modulators on hormonal treatment of breast cancer using quantum mechanical calculations and molecular docking

In this thesis, the reactive nature of Selective Estrogen Receptor Modulator (SERM) molecules has been analyzed using quantum mechanical methods. Quantum mechanical calculations were performed at DFT / M06-2X level with Stuttgart / Dresden ECP (SDD) basis set. Calculated properties include Electrostatic Potential Surface (ESP), charge distributions, electrophilic and nucleophilic regions, dipole moment, average polarity, polarity anisotropy, hyperpolarizability, electron density difference maps at boundary molecular orbital transitions, electronegativity, chemical hardness, and softness. FSP3, Topological polar surface areas, LogP and LogS values, which reveal structure activity relationships (SAR), were also calculated. The molecular docking modes of SERMs with Estrogen Receptor (ER-) were modeled, and their interactions in the docking region were analyzed. The agonist/antagonist characteristics of SERMs were analyzed depending on the docking modes of estrogen and SERMs to the active and inactive forms of Er-. Using the hierarchical grouping method, active molecules were grouped according to the similarity in their interactions with the receptor in the binding site. Finally, using quantitative structure-activity relationships (QSAR), the toxic properties of SERMs were determined.