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目的:研究一类高活性消旋化的雌激素受体调节剂与其受体间的相互作用机制.方法:分子力学优化的方法获得这类刚性的raloxifene类似物的活性构象,受体与配基间的相互作用能用分子对接程序计算.结果:化合物的R和S构型均可进入雌激素受体的结合腔.其羟基直接与受体氨基酸形成氢键,其酚环相当于雌激素的A环.活性最好的配基带有两个羟基,并已模拟雌激素A环为含16位羟基的酚环的S构型化合物.结论:消旋化对该类化合物的活性影响不大.羟基对于化合物在活性11袋中的取向及与受体的结合有着重要意义.
OBJECTIVE: To study the mechanism of interaction between a highly active racemic estrogen receptor modulator and its receptor.Methods: The active conformation of such rigid raloxifene analogues was obtained by molecular mechanics optimization, and the receptor and ligand The molecular interactions can be calculated by the molecular docking procedure.RESULTS: The R and S configurations of the compounds can both enter the binding cavity of the estrogen receptor.The hydroxyl groups directly form hydrogen bonds with the acceptor amino acids, the phenolic rings are equivalent to estrogen Ring A. The most active ligand has two hydroxyl groups and has simulated the S configuration of the estrogen A ring as a phenolic ring with a hydroxyl group of 16 Conclusion: Racemization has little effect on the activity of these compounds. The hydroxyl group is of great significance for the orientation of the compound in the active 11-pocket and its binding to the receptor.