图形和多层次序列融合学习用于预测BACE-1抑制剂的分子活性
Shaohua Zheng1, Changwang Zhang1, Youjia Chen1
1College of Physics and Information Engineering, Fuzhou University, Fuzhou 350108, China.
International journal of molecular sciences
|February 26, 2025
概括
这项研究引入了一种新的图形和多层次序列融合学习 (GSFL) 模型,以提高对阿尔茨海默病治疗的BACE-1抑制剂的预测. 该模型整合了图形和序列数据,显著提高了分子活动预测的准确性.
科学领域:
- 计算化学计算化学
- 化学信息学 化学信息学
- 药物发现 药物发现 药物发现
背景情况:
- 阿尔茨海默病 (AD) 药物开发需要有效的BACE-1抑制剂.
- 图形神经网络 (GNN) 显示出分子活动预测的前景,但缺乏序列信息.
- 为了准确预测BACE-1抑制剂活性,现有的方法需要改进.
研究的目的:
- 开发一种先进的模型来预测BACE-1抑制剂的分子活性.
- 整合基于图形和序列的分子表示,以改善预测.
- 解决GNN在捕获序列级语义信息方面的局限性.
主要方法:
- 提出了一个新的图形和多层次序列融合学习 (GSFL) 模型.
- 具有原子级注意力的GNN编码了分子图形结构.
- 具有层次关注的BiLSTM转换器编码了多层次的SMILES子字符串.
- 用ChEMBL数据集 (1548种化合物) 来预测BACE-1抑制剂活性,这些特征被合并.
主要成果:
- 该GSFL模型在预测BACE-1抑制剂活性方面实现了高准确性 (在测试组中为0.877).
- 获得的灵敏度为0.852,特异性为0.894,MCC为0.744,F1得分为0.872,PRC为0.869,AUC为0.915.4的.
- 超过了传统的计算机辅助药物设计和其他机器学习算法.
结论:
- 该GSFL模型有效地提高了BACE-1抑制剂分子活性预测的准确性.
- 图形和序列信息的融合增强了预测能力.
- 该模型显示了在阿尔茨海默病药物设计中应用的巨大潜力.
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