Geronikaki A, Druzhilovsky D, Zakharov A, Poroikov V
School of Pharmacy, Department of Pharmaceutical Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece.
SAR QSAR Environ Res. 2008 Jan-Mar;19(1-2):27-38. doi: 10.1080/10629360701843649.
Some computational tools for medicinal chemistry freely available on the Internet were compared to examine whether the results of prediction obtained with different methods coincided or not. It was shown that the correlation coefficients varied from 0.65 to 0.90 for log P (seven methods), from 0.01 to 0.73 for aqueous solubility (four methods), and from 0.19 to 0.73 for drug-likeness (three methods). While for log P estimates, reasonable average pairwise correlation was found, for aqueous solubility and drug-likeness it was rather poor. Therefore, using computational tools freely available via the Internet, medicinal chemists should evaluate their accuracy versus experimental data for particular series of compounds. In contrast to prediction of above mentioned properties, which can be done with several Internet tools, wide profiling of biological activity can be obtained only with PASS Inet (http://www.ibmc.msk.ru/PASS). PASS Inet was tested by a dozen medicinal chemists for compounds from different chemical series with various kinds of biological activity, and in the majority of cases the results of prediction coincided with the experiments. New anxiolytics, antiarrhythmics, antileishmanials, and other biologically active agents have been identified on this basis. The advantages and limitations of computer-aided predictions for medicinal chemistry via the Internet are discussed.
对一些可在互联网上免费获取的药物化学计算工具进行了比较，以检验用不同方法获得的预测结果是否一致。结果表明，对于log P（七种方法），相关系数在0.65至0.90之间；对于水溶性（四种方法），相关系数在0.01至0.73之间；对于药物相似性（三种方法），相关系数在0.19至0.73之间。虽然对于log P估计值，发现了合理的平均成对相关性，但对于水溶性和药物相似性，相关性相当差。因此，使用通过互联网免费获取的计算工具时，药物化学家应针对特定系列的化合物，将其准确性与实验数据进行评估。与上述性质的预测不同，上述性质可用几种互联网工具进行预测，而生物活性的广泛分析只能通过PASS Inet（http://www.ibmc.msk.ru/PASS）获得。十几位药物化学家对PASS Inet进行了测试，测试对象是来自不同化学系列、具有各种生物活性的化合物，在大多数情况下，预测结果与实验结果一致。在此基础上，已鉴定出新型抗焦虑药、抗心律失常药、抗利什曼原虫药及其他生物活性剂。本文讨论了通过互联网进行药物化学计算机辅助预测的优点和局限性。
