Automated simulation-based membrane protein refinement into cryo-EM data.

ABSTRACT: The resolution revolution has increasingly enabled single-particle cryogenic electron microscopy (cryo-EM) reconstructions of previously inaccessible systems, including membrane proteins-a category that constitutes a disproportionate share of drug targets. We present a protocol for using density-guided molecular dynamics simulations to automatically refine atomistic models into membrane protein cryo-EM maps. Using adaptive force density-guided simulations as implemented in the GROMACS molecular dynamics package, we show how automated model refinement of a membrane protein is achieved without the need to manually tune the fitting force ad hoc. We also present selection criteria to choose the best-fit model that balances stereochemistry and goodness of fit. The proposed protocol was used to

SUBMITTER: Yvonnesdotter L 

PROVIDER: S-EPMC10397807 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature