Side-chain-directed model and map validation for 3D Electron Cryomicroscopy

Abstract

Advances in electron cryomicroscopy allow for the building of de novo atomic models into high resolution Coulomb potential maps. While established validation metrics independently assess map quality and model geometry, methods to assess the precise fitting of an atomic model into the map and to validate the interpretation of high resolution features are less well developed. Here, we present EMRinger, which tests model-to-map agreement using side-chain dihedral-directed map density measurements. These measurements reveal local map density peaks and show that peaks located at rotameric angles are a sensitive marker of whether the backbone is correctly positioned. The EMRinger Score can be improved by model refinement, suggesting its utility as an effective model-to-map validation metric. Additionally, EMRinger sampling identifies how radiation damage alters scattering from negatively charged amino acids during data collection. EMRinger will be useful in assessing how advances in cryo-EM increase the ability to resolve and model high-resolution features.