两种雌激素受体与抑制剂作用的机制

J4 ›› 2011, Vol. 24 ›› Issue (2): 8-13.

两种雌激素受体与抑制剂作用的机制

李龙飞, 孙德福, 张少龙, 张庆刚

山东师范大学物理与电子科学学院，山东济南 250014

收稿日期:2011-01-23 出版日期:2011-04-20 发布日期:2011-04-20
作者简介:李龙飞(1986-)，男，硕士研究生，主要从事分子动力学模拟的研究
基金资助:
国家自然科学基金(10874104)；山东省自然科学基金(Z2007A05)

Function mechanism of two estrogen receptors and an inhibitor

LI Long-Fei, SUN De-Fu, ZHANG Shao-Long, ZHANG Qing-Gang

College of Physics and Electronics, Shandong Normal University, Jinan 250014, China

Received:2011-01-23 Online:2011-04-20 Published:2011-04-20

摘要/Abstract

摘要：

对雌激素受体ERα和ERβ与抑制剂244结合的体系进行了12 ns的分子动力学模拟,用MMPBSA方法计算了体系的结合自由能，抑制剂与ERα的结合自由能是-30.11 kJ/mol，与ERβ的是-33.32 kJ/mol。ERα中Met421侧链原子与抑制剂间的静电排斥作用使活性口袋周围的残基构象发生变化，导致活性区域中结合空穴变大，从而使ERα与抑制剂的亲和性降低。自由能分解计算进一步说明了各个残基对自由能的贡献。

关键词: MM-PBSA/GBSA, 结合自由能, ER抑制剂

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

中图分类号:

O641.12

李龙飞, 孙德福, 张少龙, 张庆刚. 两种雌激素受体与抑制剂作用的机制[J]. J4, 2011, 24(2): 8-13.

LI Long-Fei, SUN De-Fu, ZHANG Shao-Long, ZHANG Qing-Gang. Function mechanism of two estrogen receptors and an inhibitor[J]. J4, 2011, 24(2): 8-13.

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