Simulation-Based Methods for Model Building and Refinement in Cryoelectron Microscopy
- 30 March 2020
- journal article
- review article
- Published by American Chemical Society (ACS) in Journal of Chemical Information and Modeling
- Vol. 60 (5), 2470-2483
- https://doi.org/10.1021/acs.jcim.0c00087
Abstract
Advances in cryoelectron microscopy (cryo-EM) have revolutionized the structural investigation of large macromolecular assemblies. In this review, we first provide a broad overview of modeling methods used for flexible fitting of molecular models into cryo-EM density maps. We give special attention to approaches rooted in molecular simulations-atomistic molecular dynamics and Monte Carlo. Concise descriptions of the methods are given along with discussion of their advantages, limitations, and most popular alternatives. We also describe recent extensions of the widely used molecular dynamics flexible fitting (MDFF) method and discuss how different model-building techniques could be incorporated into new hybrid modeling schemes and simulation workflows. Finally, we provide two illustrative examples of model-building and refinement strategies employing MDFF, cascade MDFF, and RosettaCM. These examples come from recent cryo-EM studies that elucidated transcription preinitiation complexes and shed light on the functional roles of these assemblies in gene expression and gene regulation.Funding Information
- National Institute of General Medical Sciences (GM110387)
- Georgia State University
This publication has 100 references indexed in Scilit:
- Evolutionary bidirectional expansion for the tracing of alpha helices in cryo-electron microscopy reconstructionsJournal of Structural Biology, 2012
- BCL::EM-Fit: Rigid body fitting of atomic structures into density maps using geometric hashing and real space refinementJournal of Structural Biology, 2011
- Applications of the molecular dynamics flexible fitting methodJournal of Structural Biology, 2011
- Scalable molecular dynamics with NAMDJournal of Computational Chemistry, 2005
- Fourier shell correlation threshold criteriaJournal of Structural Biology, 2005
- Fitting of High-Resolution Structures into Electron Microscopy Reconstruction ImagesStructure, 2005
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004
- Normal mode based flexible fitting of high-resolution structure into low-resolution experimental data from cryo-EMJournal of Structural Biology, 2004
- Quantitative Fitting of Atomic Models into Observed Densities Derived by Electron MicroscopyJournal of Structural Biology, 1999
- VMD: Visual molecular dynamicsJournal of Molecular Graphics, 1996