Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps

• DOI: 10.7554/elife.16105
• Publication Date: 2016-07-07T11:59:54Z
• Authors: Abhishek Singharoy; Ivan Teo; Ryan McGreevy; John E Stone; Jianhua Zhao; Klaus Schulten
• Keywords: Cryo-Electron Microscopy

Two structure determination methods, based on the molecular dynamics flexible fitting (MDFF) paradigm, are presented that resolve sub-5 Å cryo-electron microscopy (EM) maps with either single structures or ensembles of such structures. The denoted cascade MDFF and resolution exchange MDFF, sequentially re-refine a search model against series progressively higher resolutions, which ends original experimental resolution. Application sequential re-refinement enables to achieve radius convergence ~25 demonstrated accurate modeling β-galactosidase TRPV1 proteins at 3.2 3.4 resolution, respectively. refinements uniquely offer map-model validation B-factor criteria inherent macromolecules studied, captured by means local root mean square fluctuations. tools described available researchers through an easy-to-use cost-effective cloud computing resource Amazon Web Services.