From mutations to mechanisms: using AlphaFold 2 to decode gentamicin resistance

Laboratory-evolved gentamicin-resistant bacteria are analysed using whole-genome sequencing and protein-structure modelling. The study focuses on mutations in elongation factor G and compares AlphaFold2 predictions with wild-type proteins. Aligning predicted EF-G structures with experimental ribosome and antibiotic-bound structures reveals how local conformational and physicochemical changes could affect drug binding. The talk examines subtle structural shifts, mutations without detectable structural changes, and the limitations of prediction alone. It presents a workflow that combines genomic evidence, AI models and experimental structures to form mechanistic hypotheses about antimicrobial resistance.