Pustaka Ilmiah Universitas Padjadjaran

Abstrak

Docking Simulation of Fevicordin into Human Receptor Estrogen

Fevicordin have similar structure to estradiol and cytotoxic in nature, thus can be developed as cancer drug. Docking method can be applied to simulate it interactions with human estrogen receptor ƒ¿ which is known involve in growth of breast cancer. Information from simulation can be used to optimize its activity on target. Docking method was validated with redocking of x-ray estradiol structure and modelled estradiol into x-ray estradiol cognate binding pocket. Fevicordin 3D structure modelled with molecular mechanic in MM+ force field, then its unique conformers modelled with molecular dynamic simulation in same force field. Each conformers docked into x-ray estradiol binding pocket (SP). Alternative pocket (AP) was searched using Q-SiteFinder software and each of fevicordinfs conformers was docked into that pocket. Validation of docking method showed that AutoDock was valid to predict binding mode of x-ray estradiol and modelled estradiol and value of both predicted Ki was in prediction range. Modelled fevicordin was a planar conformation relative to estradiol and it has three conformers which were K1, a planar form, K2 and K3, both were bend form. Conformer K2 bind well into SP relative to K1 and K3 with predicted binding free energy -9,80 kcal/mol and Ki 65,8 nM. Alternative pocket (AP) volume was 460 A3 and located in groove formed by helix 3, helix 5 and loop 1 of hERƒ¿ LBD. Conformer K3 bind well into AP relative to K1 and K2 with predicted binding free energy -8,48 kcal/mol and Ki 612 nM. Binding affinities comparison of fevicordin at SP and AP showed that fevicordinfs binding tendency into AP, thus fevicordin was predicted unable to compete with estradiol.