@article{bibcite_651,
  keywords = {molecular dynamics, Alzheimer, electric fields, AlphaFold, SAPPHIRE, disordered proteins},
  author = {P. A. Vargas-Rosales and A. DAddio and Y. Zhang and A. Caflisch},
  title = {Disrupting dimeric β-amyloid by electric fields},
  abstract = {<p>The early oligomers of the amyloid A\&$\#$946; peptide are implicated in Alzheimer\&rsquo;s disease, but their transient nature complicates the characterization of their structure and toxicity. Here, we investigate the stability of the minimal toxic species, i.e., \&$\#$946;-amyloid dimers, in the presence of an oscillating electric field. We first use deep learning (AlphaFold-multimer) for generating initial models of A\&$\#$946;42 dimers. The flexibility and secondary structure content of the models are then analyzed by multiple runs of molecular dynamics (MD). Structurally stable models are similar to ensemble representatives from microsecond-long MD sampling. Finally, we employ the validated model as the starting structure of MD simulations in the presence of an external oscillating electric field and observe a fast decay of \&$\#$946;-sheet content at high field strengths. Control simulations using the helical dimer of the 42-residue leucine zipper peptide show higher structural stability than the A\&$\#$946;42 dimer. The simulation results provide evidence that an external electric field (oscillating at 1 GHz) can disrupt amyloid oligomers which should be further investigated by experiments with brain organoids in vitro and eventually in vivo.</p>},
  year = {2023},
  journal = {ACS Physical Chemistry Au},
  volume = {3},
  pages = {456{\textendash}466},
  month = {2023 July 12},
  doi = {10.1021/acsphyschemau.3c00021},
  language = {eng},
}