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

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.

SUBMITTER: Zelnik ID 

PROVIDER: S-EPMC10122649 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature