Institute of Information Science, Academia Sinica, Taipei 11529, Taiwan.
Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Int J Mol Sci. 2023 Apr 5;24(7):6788. doi: 10.3390/ijms24076788.
Because of the growing number of clinical antibiotic resistance cases in recent years, novel antimicrobial peptides (AMPs) may be ideal for next-generation antibiotics. This study trained a Wasserstein generative adversarial network with gradient penalty (WGAN-GP) based on known AMPs to generate novel AMP candidates. The quality of the GAN-designed peptides was evaluated in silico, and eight of them, named GAN-pep 1-8, were selected by an AMP Artificial Intelligence (AI) classifier and synthesized for further experiments. Disc diffusion testing and minimum inhibitory concentration (MIC) determinations were used to identify the antibacterial effects of the synthesized GAN-designed peptides. Seven of the eight synthesized GAN-designed peptides displayed antibacterial activity. Additionally, GAN-pep 3 and GAN-pep 8 presented a broad spectrum of antibacterial effects and were effective against antibiotic-resistant bacteria strains, such as methicillin-resistant and carbapenem-resistant . GAN-pep 3, the most promising GAN-designed peptide candidate, had low MICs against all the tested bacteria. In brief, our approach shows an efficient way to discover AMPs effective against general and antibiotic-resistant bacteria strains. In addition, such a strategy also allows other novel functional peptides to be quickly designed, identified, and synthesized for validation on the wet bench.
由于近年来临床抗生素耐药病例不断增加，新型抗菌肽 (AMPs) 可能是下一代抗生素的理想选择。本研究基于已知的 AMPs 训练了一个基于 Wasserstein 生成对抗网络的梯度惩罚 (WGAN-GP)，以生成新型 AMP 候选物。通过计算机评估了 GAN 设计肽的质量，其中 8 种被 AMP 人工智能 (AI) 分类器选中，并进行了合成以进行进一步的实验。通过扩散圆盘试验和最小抑菌浓度 (MIC) 测定来鉴定合成的 GAN 设计肽的抗菌效果。这 8 种合成的 GAN 设计肽中有 7 种显示出抗菌活性。此外，GAN-pep 3 和 GAN-pep 8 具有广谱抗菌作用，对耐甲氧西林和耐碳青霉烯等抗生素的耐药菌菌株有效。作为最有前途的 GAN 设计肽候选物，GAN-pep 3 对所有测试的细菌的 MIC 均较低。总之，我们的方法为发现对抗一般和抗生素耐药菌菌株有效的 AMP 提供了一种有效的方法。此外，这种策略还可以快速设计、鉴定和合成其他新型功能肽，以便在湿实验台上进行验证。
