| Summary: | 碩士 === 國立成功大學 === 化學系碩博士在職專班 === 98 === It is known that some diseases such as breast cancer and osteoporosis are related to estrogen receptor (ER). ER is activated by its ligand, estrogens, which are steroid hormone. According to literatures the combination between ER and estrogen is based on hydrogen bonds, so theoretical calculation is applied to study these hydrogen bonds. We hope this study can help us to understand the structure.
Human estrogen, estradiol, and three estrogen-like compounds, Diethylstilbestrol, Raloxifen and 4-hydroxytamoxifen, are studied. They combine with ER-? to form 1ERE, 3ERD, 1ERR and 3ERT respectively. The XRD structures which can be downloaded from RCSB Protein Data Bank are used to construct the calculation models. First only estrogen and its surrounding groups, Arg394, Glu353, water, Leu387, and His524, which can form hydrogen bonds, are calculated. Gaussian 98 software is used and Hartree-Fock theory method, density functional theory method, and nature bond orbital analysis are applied to this study. Because Arg394 moves its position to form more hydrogen bonds to stabilize the structure, the optimized structure is not same with XRD structure.Charge distribution of the structure, and bond length, angle, stabilizing energy (E2), and orbital hybrid of Hydrogen bonds are discussed. Some donor-acceptor bonds are also found in the optimized structure.
For understanding hydrogen bonds in the XRD structure the known coordinates of atoms are fixed in the simplified structure, and only hydrogen atoms are allowed to move, but this constraint can not finish the optimization calculation. If only the relative distance between N and O atoms is fixed, the optimization calculation can be finished, and the result is similar with XRD structure.
To understand if other groups which do not form hydrogen bonds with estrogen affect the combination of estrogen and ER, the whole structure is calculated. The whole structure is divided to two parts, inner is the simplified structure described above and outer is the others. ONIOM method is applied to this calculation and AMBER method is applied to outer part. The bond length and angle of hydrogen bonds are obtained, and future studies will be continued.
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