Computational and Structural Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
J Chem Inf Model. 2022 Aug 8;62(15):3477-3485. doi: 10.1021/acs.jcim.2c00803. Epub 2022 Jul 18.
As with other pharma companies, we maintain production QSAR models of ADMET end points and update them regularly. Here, for six ADMET end points, we examine the predictions of test set molecules on multiple versions of random forest models spanning a period of 10 years. For any given end point, the predictions for the majority of molecules are similar for all model versions. However, for a small minority of molecules, the prediction shifts substantially over the span of a few versions. For most molecules that shift, the prediction becomes more accurate at later times. This Perspective investigates metrics that can help indicate which molecules will shift substantially in prediction and when the shift will occur.
与其他制药公司一样，我们维护 ADMET 终点的生产定量构效关系模型，并定期进行更新。在这里，我们针对六个 ADMET 终点，检查了测试集分子在跨越 10 年的多个随机森林模型版本上的预测。对于任何给定的终点，大多数分子的预测在所有模型版本中都是相似的。然而，对于一小部分分子，预测在几个版本的跨度内会发生很大的变化。对于大多数发生变化的分子，预测在后期会变得更加准确。本观点研究了可以帮助指示哪些分子的预测会发生很大变化以及何时发生变化的指标。
