COSMO-RS Calculations of Partition Coefficients: Different Tools for Conformational Search
COSMO-RS Calculations of Partition Coefficients: Different Tools for Conformational Search
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DOI：
10.1002/ceat.200800654
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发表时间：
2009-06-01
影响因子：
2.1
通讯作者：
Arlt, Wolfgang
中科院分区：
文献类型：
--
作者：
Buggert, Matthias;Cadena, Cesar;Arlt, Wolfgang
这项工作是鼓舞人心的日益增长的兴趣和最近的成功，基于量子力学的方法在化学工程和生命科学领域的热力学性质建模。其中，COSMO-RS模型已成为预测复杂生物相关体系相平衡的最流行的方法之一。最近，我们已经表明，正辛醇/水和胶束/水分配系数的预测质量得到改善时，加权混合物的构象被用来代表分子，从而要求进行构象分析的系统的每个组件。在本文中，不同的方法进行构象搜索进行评估。胶束/水分配系数的溶质从不同的同源系列在Triton X100的水溶液中，以及正辛醇/水分配的三种常见的药物（氨基青霉烷酸，氨苄青霉素，青霉素G）的计算和实验数据进行比较。通过HyperChem程序对置于真空中的分子进行构象分析，以及通过使用溶剂介质（正辛醇和水）中的分子动力学模拟进行构象分析。结果表明，分子动力学模拟是一个很有前途的工具进行构象分析。沿着为大的表面活性剂和药物分子提供构象异构体的可能性，该方法以现实的方式解释溶剂。胶束/水分配系数的结果表明，正辛醇是一个合理的近似的“胶束状”介质的分子动力学（MD）模拟。预测的三种青霉素的正辛醇/水分配系数与文献数据和常用的定量构效关系（QSAR）计算值吻合较好。
This work is encouraged by the growing interest and recent success of quantum mechanics-based methods in modeling of thermodynamic properties in the field of chemical engineering and life sciences. Among those, the COSMO-RS model has become one of the most popular methods to predict phase equilibria in complex bio-related systems. Recently, we have shown that the quality of predictions of n-octanol/water and micelle/water partition coefficients is improved when the weighted mixtures of conformers are used to represent molecules, thereby demanding that the conformation analysis is performed for each component of the system. In this paper, different methods for performing the conformational search are evaluated. Micelle/water partition coefficients of solutes from different homologous series in aqueous solutions of Triton X100 as well as the n-octanol/ water partitioning of three common drugs (aminopinicillanic acid, ampicillin, and penicillin G) are calculated and compared with experimental data. Conformational analysis is made by the HyperChem program for the molecules placed in vacuum as well as by using the molecular dynamics simulation in a solvent medium (n-octanol and water). It is demonstrated that molecular dynamics simulation is a promising tool to conduct conformational analysis. Along with the possibility of providing the conformers for large Surfactant and pharmaceutical molecules, the method accounts for the solvent in a realistic manner. The results for micelle/water partition coefficients illustrate that n-octanol is a reasonable approximation for the "micelle-like" medium in molecular dynamics (MD) simulations. Predicted n-octanol/water partition coefficients of three penicillins are in a good agreement with literature data and values Calculated by a common quantitative structure-activity relationship (QSAR).