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机器学习模型用于预测细胞染色体P450 2B6抑制剂和基质
Longqiang Li1, Zhou Lu1, Guixia Liu1
1Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
机器学习模型可以准确地预测细胞染色体P450 2B6 (CYP2B6) 抑制剂和基质. 这些预测工具通过识别涉及CYP2B6代谢的潜在药物相互作用,有助于早期药物发现.
科学领域:
- 药物基因组学 药物基因组学
- 计算化学的计算化学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 细胞染色体P450 2B6 (CYP2B6) 代谢了大约7%的市场药物.
- 监管指南 (FDA) 要求评估药物相互作用与主要药物代谢酶,如CYP2B6.
- 准确预测CYP2B6抑制剂和基质对于有效的药物开发至关重要.
研究的目的:
- 开发和验证用于预测CYP2B6抑制剂和基质的机器学习模型.
- 确定与CYP2B6抑制和基质活性相关的关键结构特征.
- 为开发的预测模型建立适用性领域.
主要方法:
- 开发传统的机器学习和深度学习模型.
- 使用十倍交叉验证,测试集和外部验证集评估模型性能.
- 亚结构碎片分析和信息获取用于特征识别.
- 定义模型适用性领域的非参数方法.
主要成果:
- 最好的CYP2B6抑制剂模型实现了AUC值为0.95 (交叉验证) 和0.75 (测试组).
- 最好的CYP2B6基质模型实现了AUC值为0.93 (交叉验证) 和0.90 (测试组).
- 确定了影响CYP2B6相互作用的显著的亚结构碎片.
结论:
- 开发的机器学习模型显示了对CYP2B6抑制剂和基质的强大预测性能.
- 已识别的亚结构片段为CYP2B6的药物相互作用提供了洞察力.
- 这些模型和发现可以通过预测潜在的CYP2B6负债来促进早期药物发现.
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