Atomic-accuracy models from 4.5-Å cryo-electron microscopy data with density-guided iterative local refinement

Nat Methods. 2015 Apr;12(4):361-365. doi: 10.1038/nmeth.3286. Epub 2015 Feb 23.


We describe a general approach for refining protein structure models on the basis of cryo-electron microscopy maps with near-atomic resolution. The method integrates Monte Carlo sampling with local density-guided optimization, Rosetta all-atom refinement and real-space B-factor fitting. In tests on experimental maps of three different systems with 4.5-Å resolution or better, the method consistently produced models with atomic-level accuracy largely independently of starting-model quality, and it outperformed the molecular dynamics-based MDFF method. Cross-validated model quality statistics correlated with model accuracy over the three test systems.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chemistry, Physical / methods*
  • Cryoelectron Microscopy*
  • Models, Molecular*
  • Monte Carlo Method
  • Proteins / chemistry*


  • Proteins