@article{3026,
  keywords = {Kinetics, Peptides, Molecular Dynamics Simulation, Protein Stability},
  author = {Caitlin Allen and Maria Chen and Alexander Trick and Dan Le and Andrew Ferguson and A James Link},
  title = {Thermal Unthreading of the Lasso Peptides Astexin-2 and Astexin-3.},
  abstract = { <p>Lasso peptides are a class of knot-like polypeptides in which the C-terminal tail of the peptide threads through a ring formed by an isopeptide bond between the N-terminal amine group and a side chain carboxylic acid. The small size (\~{}20 amino acids) and simple topology of lasso peptides make them a good model system for studying the unthreading of entangled polypeptides, both with experiments and atomistic simulation. Here, we present an in-depth study of the thermal unthreading behavior of two lasso peptides astexin-2 and astexin-3. Quantitative kinetics and energetics of the unthreading process were determined for variants of these peptides using a series of chromatography and mass spectrometry experiments and biased molecular dynamics (MD) simulations. In addition, we show that the Tyr15Phe variant of astexin-3 unthreads via an unprecedented "tail pulling" mechanism. MD simulations on a model ring-thread system coupled with machine learning approaches also led to the discovery of physicochemical descriptors most important for peptide unthreading.</p> },
  year = {2016},
  journal = {ACS Chem Biol},
  volume = {11},
  pages = {3043-3051},
  month = {2016 Nov 18},
  issn = {1554-8937},
  doi = {10.1021/acschembio.6b00588},
  language = {eng},
}