Effects of Point Mutations on the Binding Energies of Estrogen Receptor with Estradiol

Abstract

We have studied the molecular mechanism for the binding between estrogen receptor and estradiol using ab initio methods. To examine the validity of in silico analysis of mutation effects, we made point mutations of receptor employed in experiments, and compared the calculated results for the binding energies with experimental data. We performed the calculations at the HF/STO-3G and MP2/STO-3G levels by using the Fragment Molecular Orbital (FMO) method. The calculated results for three of six mutants qualitatively agreed with experimental data. However, the other three examples failed to reproduce the experimental data. We discussed the reasons for these discrepancies.