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Updated: Aug 2, 2025

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
Computational design and molecular dynamics simulations suggest the mode of substrate binding in ceramide synthases
Iris D Zelnik1, Beatriz Mestre1, Jonathan J Weinstein1
1Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 76100, Israel.
Abstract:
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.
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