Artificial intelligence in protein-based detection and inhibition of AMR pathways.

Antimicrobial Resistance (AMR) is a global concern demanding high-throughput and precise AMR surveillance strategies. This review provides a comprehensive list of Artificial Intelligence (AI) driven frameworks widely employed in the early detection, structural characterization, and designing of novel inhibitors to block the resistance pathways critical for AMR. Deep learning algorithms including DeepGO, DeepGOPlus, DeepGO-SE, PFresGO, DPFunc, ProtENN and graph-based architectures of GraphSite, GrASP enables precise functional annotation of resistance-associated proteins. AI-guided protein modeling performed by AlphaFold, RoseTTAFold, ProtGPT-2, ESMFold etc. generates high resolution 3D conformations, further utilized in performing molecular docking via tools like AutoDock, DeepDocking and DeepChem and analyzed with tools like DeepDriveMD, TorchMD, and PRITHVI, which can perform real-time molecular dynamics simulations. Identification of relevant resistant biomarkers from mass-spectrometry profiles can also be achieved with the help of DeepNovo, Casanovo, or Prosit. Tools like DeepARG, HMD-ARG, and BacEffluxPred enables identification of unannotated resistance genes from metagenomic samples. Natural Language Processing (NLP) and Large Language-based models (LLM) facilitate identification of resistant determinants via literature mining enabling regulatory network mapping and rational inhibitor design. Furthermore, AI-mediated de-novo inhibitor design is achieved using Variational Autoencoders (VAE), Generative Adversarial Networks (GAN), diffusion and flow-matching based frameworks serve as potential options for enhancing diagnostic interventions against resistant phenotypes. AI-based protein-protein interaction predictors include DeepInteract, Pred_PPI, PLIP, DeepAIPs-Pred, DeepAIPs-SFLA, SBSM-Pro, Deep Stacked-AVPs, and pNPs-CapsNet help in understanding how resistance proteins interact with each other enabling precise identification of AMR-modulating peptides and supports the modeling of novel antibiotics for blocking interactions and disrupting resistance pathways.