title: Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes.
abstract: The rise of the computer as a powerful tool for model building and refinement has revolutionized the field of structure determination for large biomolecular systems. Despite the wide availability of robust experimental methods capable of resolving structural details across a range of spatiotemporal resolutions, computational hybrid methods have the unique ability to integrate the diverse data from multimodal techniques such as X-ray crystallography and electron microscopy into consistent, fully atomistic structures. Here, commonly employed strategies for computational real-space structural refinement are reviewed, and their specific applications are illustrated for several large macromolecular complexes: ribosome, virus capsids, chemosensory array, and photosynthetic chromatophore. The increasingly important role of computational methods in large-scale structural refinement, along with current and future challenges, is discussed.
authors.affiliation: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.|Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
authors.forename: Boon Chong
authors.initials: BC
authors.lastname: Goh
authors.affiliation: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.|Energy Biosciences Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Hadden
authors.affiliation: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.|Energy Biosciences Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Bernardi
authors.affiliation: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Singharoy
authors.affiliation: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
authors.forename: Ryan
authors.initials: R
authors.lastname: McGreevy
authors.affiliation: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
authors.forename: Till
authors.initials: T
authors.lastname: Rudack
authors.affiliation: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.|Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
authors.forename: C Keith
authors.initials: CK
authors.lastname: Cassidy
authors.affiliation: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.|Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.|Energy Biosciences Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.|Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.|Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; email: kschulte@ks.uiuc.edu.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
mesh_terms: D020130:Bacterial Chromatophores / Q000737:chemistry; D002213:Capsid / Q000737:chemistry; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry*; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry
chemical_list: D046911:Macromolecular Substances; D046912:Multiprotein Complexes
keywords: cryo-EM; flexible fitting; hybrid methods; integrative modeling; molecular dynamics; simulation