论文标题
FMO相互作用能量在17 $β$ - 雌二醇，17 $α$ - 雌二醇和人雌激素受体$α$之间
FMO Interaction Energy between 17$β$-Estradiol, 17$α$-Estradiol and Human Estrogen Receptor $α$
论文作者
论文摘要
雌激素受体是一种由天然类固醇激素17 $β$ - 雌二醇（E2）激活的核激素受体。进行了片段分子轨道（FMO）计算，这使我们能够在E2、17 $α$ -Estradiol（17 $α$ -e2）和人类雌激素受体$α$α$ a $ cog figand-figand结合域之间获得相互作用能（$ e_ {int} $）。在水性介质中，MP2/6-31G（d）$ e_ {int} $对于E2的-88.52 kcal/mol为-17 $α$ -e2的-78.73 kcal/mol。在配体和所有周围疏水残基之间观察到了有吸引力的分散相互作用。在结合位点发现了水分子，并在配体和GLU 353和他的524个残基之间观察到了强烈的静电相互作用。基本动力学表明，E2从某种意义上适应结合位点及其运动与整个受体同步。而与E2相比，其运动幅度更大的17 $α$ -e2却打扰了结合位点。也许正常底物的这一特征是生物学功能的必要条件。另一个重要的要求与结合位点的水分子数量有关。因此，$ e_ {int} $中的负值是必要但不是足够的条件，因为还必须考虑满足确保生物学反应的所有要求的构象种群。
The estrogen receptor is a nuclear hormone receptor activated by the natural steroid hormone 17$β$-estradiol (E2). Fragment molecular orbital (FMO) calculations were performed which allowed us to obtain the interaction energy ($E_{int}$) between E2, 17$α$-estradiol (17$α$-E2) and the human estrogen receptor $α$ ligand-binding domain. In aqueous media the MP2/6-31G(d) $E_{int}$ was of -88.52 kcal/mol for E2 and -78.73 kcal/mol for 17$α$-E2. Attractive dispersion interactions were observed between ligands and all surrounding hydrophobic residues. Water molecules were found at the binding site and strong attractive electrostatic interactions were observed between the ligands and the Glu 353 and His 524 residues. The essential dynamics revealed that E2 adapts to the binding site and its motion, in a sense, synchronizes with the whole receptor; while 17$α$-E2, with its motion of greater amplitude compared to E2, disturbs the binding site. Perhaps this feature of the normal substrate is a necessary condition for biological function. Another important requirement relates to the number of water molecules at the binding site. Therefore, negative values in $E_{int}$ is a necessary but not sufficient condition since, it is also necessary to consider the conformers population that fulfill all the requirements that ensure a biological response.
