Xie Peilin, Yao Lantian, Guan Jiahui, Chung Chia-Ru, Zhao Zhihao, Long Feiyu, Sun Zhenglong, Lee Tzong-Yi, Chiang Ying-Chih
Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, China.
School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, China.
Protein Sci. 2025 Jul;34(7):e70087. doi: 10.1002/pro.70087.
Many antimicrobial peptides (AMPs) function by disrupting the cell membranes of microbes. While this ability is crucial for their efficacy, it also raises questions about their safety. Specifically, the membrane-disrupting ability could lead to hemolysis. Traditionally, the hemolytic activity of AMPs is evaluated through experiments. To reduce the cost of assessing the safety of an AMP as a drug, we introduce ConsAMPHemo, a two-stage framework based on deep learning. ConsAMPHemo performs conventional binary classification of the hemolytic activities of AMPs and predicts their hemolysis concentrations through regression. Our model demonstrates excellent classification performance, achieving an accuracy of 99.54%, 82.57%, and 88.04% on three distinct datasets, respectively. Regarding regression prediction, the model achieves a Pearson correlation coefficient of 0.809. Additionally, we identify the correlation between features and hemolytic activity. The insights gained from this work shed light on the underlying physics of the hemolytic nature of an AMP. Therefore, our study contributes to the development of safer AMPs through cost-effective hemolytic activity prediction and by revealing the design principles for AMPs with low hemolytic toxicity. The codes and datasets of ConsAMPHemo are available at https://github.com/Cpillar/ConsAMPHemo.
许多抗菌肽(AMPs)通过破坏微生物的细胞膜发挥作用。虽然这种能力对其功效至关重要,但也引发了对其安全性的质疑。具体而言,膜破坏能力可能导致溶血。传统上,通过实验评估AMPs的溶血活性。为了降低评估一种AMPs作为药物的安全性成本,我们引入了ConsAMPHemo,这是一个基于深度学习的两阶段框架。ConsAMPHemo对AMPs的溶血活性进行传统的二元分类,并通过回归预测其溶血浓度。我们的模型展示了出色的分类性能,在三个不同的数据集上分别达到了99.54%、82.57%和88.04%的准确率。关于回归预测,该模型的皮尔逊相关系数为0.809。此外,我们确定了特征与溶血活性之间的相关性。从这项工作中获得的见解揭示了AMPs溶血性质的潜在物理原理。因此,我们的研究通过经济高效的溶血活性预测以及揭示低溶血毒性AMPs的设计原则,为开发更安全的AMPs做出了贡献。ConsAMPHemo的代码和数据集可在https://github.com/Cpillar/ConsAMPHemo获取。