OmegAMP用生成模型精准设计抗菌肽,实验成功率高达96%。
OmegAMP: Targeted AMP Discovery via Biologically Informed Generation
- 基于扩散模型,通过生物信息编码实现性质与活性的精细控制。
- 25个候选肽中24个有效,对多重耐药菌也具活性。
- 适合药物研发人员,尤其关注抗耐药菌的新药设计。
基于深度学习的抗菌肽(AMP)发现面临可控性差、难以高效建模抗菌特性以及实验命中率低等挑战。为此,我们提出OmegAMP框架,通过基于扩散的生成模型结合新颖的条件机制,实现对目标理化性质和特定活性谱(包括物种特异性)的细粒度控制。该框架引入生物信息学驱动的编码空间,显著提升生成性能。同时,采用新型合成数据增强策略训练分类器以过滤AMP,大幅降低假阳性率,提高实验成功率。体外实验表明,OmegAMP在AMP发现流程的关键阶段达到领先水平;我们测试了25个候选肽,其中24个(96%)表现出抗菌活性,甚至对多重耐药菌株有效。研究结果凸显OmegAMP在对抗抗菌耐药性方面的巨大潜力。
原文摘要 · Abstract (English)
Deep learning-based antimicrobial peptide (AMP) discovery faces critical challenges such as limited controllability, lack of representations that efficiently model antimicrobial properties, and low experimental hit rates. To address these challenges, we introduce OmegAMP, a framework designed for reliable AMP generation with increased controllability. Its diffusion-based generative model leverages a novel conditioning mechanism to achieve fine-grained control over desired physicochemical properties and to direct generation towards specific activity profiles, including species-specific effectiveness. This is further enhanced by a biologically informed encoding space that significantly improves overall generative performance. Complementing these generative capabilities, OmegAMP leverages a novel synthetic data augmentation strategy to train classifiers for AMP filtering, drastically reducing false positive rates and thereby increasing the likelihood of experimental success. Our in silico experiments demonstrate that OmegAMP delivers state-of-the-art performance across key stages of the AMP discovery pipeline, enabling us to achieve an unprecedented success rate in wet lab experiments. We tested 25 candidate peptides, 24 of them (96%) demonstrated antimicrobial activity, proving effective even against multi-drug resistant strains. Our findings underscore OmegAMP's potential to significantly advance computational frameworks in the fight against antimicrobial resistance.
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