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DTSTAMP:20260829T114740Z
UID:2660209b-d8c5-4d67-83c3-7ca085dba904
DTSTART:20260904T090000Z
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DESCRIPTION:The emergence of antimicrobial resistance poses a major challen
 ge to global health\, yet the molecular mechanisms underlying resistance o
 ften remain incompletely understood. In this webinar\, I will present a ca
 se study from my PhD research investigating the genetic and structural bas
 is of gentamicin resistance in experimentally evolved bacterial mutants.\n
 \nThe project involved generating gentamicin-resistant mutants in the labo
 ratory\, performing whole-genome sequencing to identify resistance-associa
 ted mutations\, and characterising the resulting protein variants. While m
 utations were identified across several proteins\, the primary focus was o
 n elongation factor G (EF-G)\, a key component of the bacterial translatio
 n machinery.\n\nTo investigate the structural consequences of these mutati
 ons\, AlphaFold2 was used to predict mutant protein structures and compare
  them with their wild-type counterparts. Structural alignments revealed th
 at some mutations produced subtle conformational shifts in domain IV of EF
 -G\, an extended region located near the gentamicin-binding site on the ri
 bosome\, while other mutations showed little or no detectable structural c
 hange.\n\nTo place these findings into a functional context\, experimental
  ribosome structures from the Protein Data Bank were integrated with Alpha
 Fold predictions. By superimposing structures of EF-G-bound ribosomes and 
 gentamicin-bound ribosomes\, a composite structural model was generated\, 
 enabling the spatial relationship between resistance-associated mutations 
 and the antibiotic-binding site to be examined. These analyses provided me
 chanistic insights into how specific mutations may reduce gentamicin bindi
 ng through local structural and physicochemical effects.\n\nThe webinar wi
 ll discuss the opportunities and limitations of using AlphaFold to investi
 gate the structural consequences of genomic variation\, the challenges of 
 interpreting subtle structural differences\, and the importance of integra
 ting AI-predicted models with experimental structural data to generate bio
 logically meaningful hypotheses.\n\n_This event is part of a broader webin
 ar series on user cases of the AlphaFold resources. For more information a
 bout the series and its webinars\, please visit the following link: _[_Al
 phaFold in practice: research use cases | EMBL-EBI Training_](https://trai
 ningcontent.embl.org/alphafold-practice-research-use-cases)
LOCATION:\, 
SUMMARY:From mutations to mechanisms: using AlphaFold 2 to decode gentamici
 n resistance
URL;VALUE=URI:https://www.ebi.ac.uk/training/events/mutations-mechanisms-us
 ing-alphafold-2-decode-gentamicin-resistance
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