预测和解释:通过人工智能转化药物发现,以实现高精度的受体-连接体相互作用建模和结合分析
Nissrine Hatibi1, Hassan Ait Benhassou2, Mounia Abik3
1Ecole Nationale Supérieure d'Informatique et d'Analyse des Systèmes (ENSIAS), Mohammed V University in Rabat, Rabat, Morocco; Prevention and Therapeutics Center, Moroccan Foundation of Advanced Science Innovation and Research (MAScIR), Mohammed VI Polytechnic University (UM6P), Benguerir, Morocco.
Computers in biology and medicine
|May 17, 2025
概括
这项研究引入了一种机器学习框架,用于预测受体-连接体相互作用,加速药物发现. 分子表示的早期融合显著提高了预测准确性,并确定了关键的结合特征.
科学领域:
- 计算化学是一种计算化学.
- 药物发现 药物发现
- 机器学习 机器学习
背景情况:
- 制药药物开发在预测受体-连接体相互作用方面面临挑战,影响有效性和安全性.
- 预测这些相互作用的传统方法往往是缓慢和昂贵的.
- 有效的计算方法对于加速药物发现管道至关重要.
研究的目的:
- 开发和验证一个机器学习框架,用于准确预测对接分数.
- 整合多样化的分子表示,以提高预测性能.
- 为了提高预测的可解释性和理解绑定动态.
主要方法:
- 开发了一个机器学习框架,集成了Lipinski描述符,指纹和基于图形的分子表示.
- 实施并比较了早期融合 (特征级) 和晚期融合 (决策级) 战略.
- 应用局部可解释的模型不可知解释 (LIME) 用于特征重要性分析.
主要成果:
- 与其他方法相比,早期的核聚变模型显示出更高的预测准确性和稳定性.
- 通过LIME识别了影响对接分数的关键物理化学和结构特征.
- 使用生物信息学工具和3D可视化验证了框架的可靠性和生物可信性.
结论:
- 将多尺度分子表示与机器学习集成,可以提高对受体-连接体相互作用的预测.
- 开发的框架通过使候选药物的数据驱动优先级能够加速治疗开发.
- 该方法提供了对联体受体结合机制的宝贵见解,有助于设计复杂疾病的有效治疗方法.
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