Abstract:

       We performed 12 ns molecular dynamics simulation for estrogen receptor ERα and ERβ and inhibitor 244. We also calculated their binding free energy with the method of MMPBSA. Such energy of inhibitor 244 and receptor ERα is -30.11 kJ/mol, and the energy of inhibitor 244 and receptor ERβ is -33.32 kJ/mol. Electrostatic repulsion between Met421 side chain in of ERα and the inhibitor changes the conformation of Met421 Leu346 and Phe425. This causes bigger binding cavity and further decreases the binding of ERα and the inhibitor. Free energy decomposition calculation indicates the contribution of individual residue to the free energy.

Key words: MM-PBSA/GBSA, binding free energy, ER inhibitor