Ligand-Based Site of Metabolism Prediction for Cytochrome P450 2D6

A ligand-based method based on the SMARTCyp approach that predicts the sites of cytochrome P450 2D6-mediated metabolism of druglike molecules has been developed. The method uses only two descriptors besides the reactivity from SMARTCyp: the distance to a protonated nitrogen atom and the distance to the end of the molecule. Hence, the site of metabolism is predicted directly from the 2D structure of a molecule, without requiring calculation of electronic properties or generation of 3D structures. Testing on an independent test set gives an area under the curve value of 0.94, and a site of metabolism is found among the top two ranked atoms for 91% of the compounds.

本研究开发了一种基于配体的方法（ligand-based method），该方法依托SMARTCyp框架，用于预测细胞色素P450 2D6（cytochrome P450 2D6）介导的类药物分子代谢位点。该模型仅需使用两类描述符，外加SMARTCyp输出的反应性特征：即至质子化氮原子的距离与至分子末端的距离。因此，无需计算电子性质或生成三维结构，即可直接通过分子的二维结构预测其代谢位点。在独立测试集上的测试结果表明，该模型的曲线下面积（area under the curve）值为0.94，且对于91%的受试化合物，其代谢位点可在排名前两位的原子中被成功识别。