...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Medicinal Chemistry >Rational determination of transfer free energies of small drugs across the water-oil interface.
【24h】

Rational determination of transfer free energies of small drugs across the water-oil interface.

机译：合理确定小药物在水-油界面上的转移自由能。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The application of statistical simulations to the estimation of transfer free energies of pharmacologically relevant organic molecules is reported. Large-scale molecular dynamics simulations have been carried out on a series of four solutes, viz. antipyrine, caffeine, ganciclovir, and alpha-D-glucose, at the water-dodecane interface as a model of a biological water-membrane interfacial system. Agreement with experimentally determined partition coefficients is remarkable, demonstrating that free energy calculations, when executed with appropriate protocols, have reached the maturity to predict thermodynamic quantities of interest to the pharmaceutical world. The computational effort that warrants accurate, converged free energies remains, however, in large measure, incompatible with the high-throughput exploration of large sets of pharmacologically active drugs sought by industrial settings. Compared to the cost-effective, fast estimation of simple partition coefficients, the present free energy calculations, nevertheless, offer a far more detailed information about the underlying energetics of the system when the solute is translocated across the water-dodecane interface, which can be valuable in the context of de novo drug design.
机译：据报道统计模拟在药理学上相关的有机分子的转移自由能的估计中的应用。已经对一系列四种溶质进行了大规模的分子动力学模拟。在水-十二烷界面处的安替比林，咖啡因，更昔洛韦和α-D-葡萄糖，作为生物水-膜界面系统的模型。与实验确定的分配系数的一致性非常显着，这表明当使用适当的方案执行时，自由能计算已经成熟，可以预测制药界感兴趣的热力学量。但是，在很大程度上，保证精确的，会聚的自由能的计算工作仍然与工业环境中寻求的大量药理活性药物的高通量探索不兼容。与成本有效的快速估算简单分配系数相比，当前的自由能计算仍然提供了有关当溶质跨水-十二烷界面转移时系统潜在能量的更详细的信息。在从头药物设计的背景下很有价值。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号