Molecular Modeling of the Interactions between Carborane-Containing Analogs of Indomethacin and Cyclooxygenase-2
Molecular Modeling of the Interactions between Carborane-Containing Analogs of Indomethacin and Cyclooxygenase-2
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DOI：
10.1021/acs.jcim.7b00113
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发表时间：
2017-07
影响因子：
5.6
通讯作者：
M. Sárosi;W. Neumann;T. Lybrand;E. Hey‐Hawkins
中科院分区：
文献类型：
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作者：
M. Sárosi;W. Neumann;T. Lybrand;E. Hey‐Hawkins
进行了分子模拟研究，以深入了解结合模式和相互作用的碳硼烷衍生物的吲哚美辛甲酯与环氧合酶-2（考克斯-2）亚型，并评估预测能力的计算工具可用于研究碳硼烷，一类独特的药效团。对接模拟能够识别正确的结合模式，并以令人鼓舞的质量再现实验结合亲和力趋势。然而，对接结果需要通过广泛和资源密集型的量子化学计算来验证，如果没有实验数据的支持，理论结果的解释就不会简单明了。将完整的受体和配体灵活性纳入含碳硼烷药物分子的分子建模中可能会产生更明确的结果，但目前由于缺乏适当的碳硼烷力场参数而受到阻碍。
Molecular modeling studies were performed in order to gain insight into the binding mode and interaction of carborane-containing derivatives of indomethacin methyl ester with the cyclooxygenase-2 (COX-2) isoform, and to assess the predictive capability of the computational tools available for studying carboranes, a unique class of pharmacophores. Docking simulations were able to identify the correct binding mode and reproduced the experimental binding affinity trends with encouraging quality. Nevertheless, the docking results needed to be verified through extensive and resource-intensive quantum chemical calculations, and the interpretation of the theoretical results would not have been straightforward without the supporting experimental data. The inclusion of full receptor and ligand flexibility into the molecular modeling of carborane-containing drug molecules may yield more definitive results, but is currently hindered by the lack of appropriate carborane force field parameters.