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Computational design and molecular dynamics simulations suggest the mode of substrate binding in ceramide synthases.

Iris D ZelnikBeatriz MestreJonathan Yaacov WeinsteinTamir DingjanStav IzrailovShifra Ben-DorSarel Jacob FleishmanAnthony H Futerman
Published in: Nature communications (2023)
Until now, membrane-protein stabilization has relied on iterations of mutations and screening. We now validate a one-step algorithm, mPROSS, for stabilizing membrane proteins directly from an AlphaFold2 model structure. Applied to the lipid-generating enzyme, ceramide synthase, 37 designed mutations lead to a more stable form of human CerS2. Together with molecular dynamics simulations, we propose a pathway by which substrates might be delivered to the ceramide synthases.
Keyphrases
  • molecular dynamics simulations
  • molecular docking
  • endothelial cells
  • machine learning
  • deep learning
  • induced pluripotent stem cells
  • fatty acid
  • neural network
  • structural basis