机器学习模型用于预测素1受体的连接物结合亲和力
Vanessa Y Zhang1,2,3, Shayna L O'Connor1,2, William J Welsh4
1Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University and Rutgers Biomedical Health Sciences, Piscataway, NJ, USA.
Artificial intelligence chemistry
|March 13, 2024
概括
研究人员开发了对素1受体 (OX1R) 配体的预测定量结构-活性关系 (QSAR) 模型. 这种方法确定了两种FDA批准的药物作为潜在的OX1R配体,有助于新药的发现.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 计算化学计算化学
背景情况:
- 素1受体 (OX1R) 是一种与G蛋白结合的受体,涉及各种生理过程.
- 选择性OX1R对抗剂对诸如寻找药物和过度饮食等行为障碍有前途.
- 由于缺乏已批准的药物,临床上需要新型选择性OX1R抗剂.
研究的目的:
- 开发高预测性定量结构-活性关系 (QSAR) 模型,用于素1受体 (OX1R) 配体.
- 通过虚拟查,识别新的OX1R配体,包括潜在的药物候选物.
- 为未来的药物发现工作建立一个强大的QSAR建模框架,针对OX1R.
主要方法:
- 通过严格的标准,对1300多个OX1R配体的综合数据集进行了策划.
- 使用具有优化的超参数和12个选定的二维分子描述器的随机森林机器学习算法.
- 用5倍交叉验证的递归特征消除用于描述符选择和模型验证.
- 使用开发的QSAR模型,对DrugBank数据库进行了虚拟选.
- 使用放射性标记的OX1R结合试验证实了潜在的OX1R配体.
主要成果:
- 成功开发了OX1R配体的高预测性QSAR模型.
- 该QSAR模型显示出高预测性,并通过外部测试集和丰富性研究进行验证.
- 虚拟查确定了isavuconazole和cabozantinib,两种FDA批准的药物,作为潜在的OX1R配体.
- 结合性试验证实了 isavuconazole 和 cabozantinib 与 OX1R 的相互作用.
结论:
- 这项研究为OX1R配体的大型,多样化的数据集提供了第一个高度预测的QSAR模型.
- 开发的QSAR模型是发现和设计新型OX1R向化合物的宝贵工具.
- 鉴定FDA批准的药物作为潜在的OX1R配体,为治疗开发开辟了新的途径.
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