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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.

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2016-07-05
2024-05-27
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Literature Cited

  1. Abrams C, Bussi G. 1.  2013. Enhanced sampling in molecular dynamics using metadynamics, replica-exchange, and temperature-acceleration. Entropy 16:163–99 [Google Scholar]
  2. Adams PD, Afonine PV, Grosse-Kunstleve RW, Read RJ, Richardson JS. 2.  et al. 2009. Recent developments in phasing and structure refinement for macromolecular crystallography. Curr. Opin. Struct. Biol. 9:566–72 [Google Scholar]
  3. Adams PD, Baker D, Brunger AT, Das R, DiMaio F. 3.  et al. 2013. Advances, interactions, and future developments in the CNS, Phenix, and Rosetta structural biology software systems. Annu. Rev. Biophys. 42:265–87 [Google Scholar]
  4. Agrawal RK, Heagle AB, Penczek P, Grassucci RA, Frank J. 4.  1999. EF-G-dependent GTP hydrolysis induces translocation accompanied by large conformational changes in the 70S ribosome. Nat. Struct. Biol. 6:643–47 [Google Scholar]
  5. Al-Bayatti KK, Takemoto JY. 5.  1981. Phospholipid topography of the photosynthetic membrane of Rhodopseudomonas sphaeroides. Biochemistry 20:5489–95 [Google Scholar]
  6. Alber F, Dokudovskaya S, Veenhoff LM, Zhang W, Kipper J. 6.  et al. 2007. Determining the architectures of macromolecular assemblies. Nature 450:683–94 [Google Scholar]
  7. Alber F, Dokudovskaya S, Veenhoff LM, Zhang W, Kipper J. 7.  et al. 2007. The molecular architecture of the nuclear pore complex. Nature 450:695–701 [Google Scholar]
  8. Arnold K, Bordoli L, Kopp J, Schwede T. 8.  2006. The Swiss-model workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22:195–201 [Google Scholar]
  9. Asano S, Fukuda Y, Beck F, Aufderheide A, Förster F. 9.  et al. 2015. A molecular census of 26S proteasomes in intact neurons. Science 347:439–42 [Google Scholar]
  10. Bashan A, Yonath A. 10.  2011. Ribosome crystallography: from early evolution to contemporary medical insights. Ribosomes 1:3–18 [Google Scholar]
  11. Bartesaghi A, Matthies D, Banerjee S, Merk A, Subramaniam S. 11.  2014. Structure of β-galactosidase at 3.2 Å resolution obtained by cryo-electron microscopy. PNAS 111:11709–14 [Google Scholar]
  12. Bartesaghi A, Merk A, Banerjee S, Matthies D, Wu X. 12.  et al. 2015. 2.2 Å resolution cryo-EM structure of β-galactosidase in complex with a cell-permeant inhibitor. Science 348:1147–51Acquisition of the highest-resolution cryo-EM density map as of April 2016. [Google Scholar]
  13. Barty A, Küpper J, Chapman HN. 13.  2013. Molecular imaging using X-ray free-electron lasers. Annu. Rev. Phys. Chem. 64:415–35 [Google Scholar]
  14. Batista PR, Costa MGDS, Pascutti PG, Bisch PM, de Souza W. 14.  2011. High temperatures enhance cooperative motions between CBM and catalytic domains of a thermostable cellulase: mechanism insights from essential dynamics. Phys. Chem. Chem. Phys. 13:13709–20 [Google Scholar]
  15. Begley CG, Ellis LM. 15.  2012. Drug development: Raise standards for preclinical cancer research. Nature 483:531–33 [Google Scholar]
  16. Bernardi RC, Melo MCR, Schulten K. 16.  2015. Enhanced sampling techniques in molecular dynamics simulations of biological systems. Biochim. Biophys. Acta 1850:872–77 [Google Scholar]
  17. Bilwes A, Alex L, Crane B, Simon M. 17.  1999. Structure of CheA, a signal-transducing histidine kinase. Cell 96:131–41 [Google Scholar]
  18. Briegel A, Li X, Bilwes AM, Hughes KT, Jensen GJ, Crane BR. 18.  2012. Bacterial chemoreceptor arrays are hexagonally packed trimers of receptor dimers networked by rings of kinase and coupling proteins. PNAS 109:3766–71 [Google Scholar]
  19. Briegel A, Ortega DR, Tocheva EI, Wuichet K, Li Z. 19.  et al. 2009. Universal architecture of bacterial chemoreceptor arrays. Nat. Rev. Mol. Cell Biol. 106:17181–86 [Google Scholar]
  20. Brown A, Shao S, Murray J, Hegde RS, Ramakrishnan V. 20.  2015. Structural basis for stop codon recognition in eukaryotes. Nature 524:493–96 [Google Scholar]
  21. Brünger AT.21.  1992. The free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature 355:472–74 [Google Scholar]
  22. Brünger AT, Adams PD, Clore GM, DeLano WL, Gros P. 22.  et al. 1998. Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr. D 54:905–21 [Google Scholar]
  23. Brünger AT, Kuriyan J, Karplus M. 23.  1987. Crystallographic R factor refinement by molecular dynamics. Science 235:458–60 [Google Scholar]
  24. Bush DL, Monroe EB, Bedwell GJ, Prevelige PE, Phillips JM, Vogt VM. 24.  2014. Higher order structure of the Rous sarcoma virus SP assembly domain. J. Virol. 88:5617–29 [Google Scholar]
  25. Carroll MD, Hadzic I, Katsak WA. 25.  2012. 3D rendering in the cloud. Bell Labs Technical J. 17:55–66 [Google Scholar]
  26. Cartron ML, Olsen JD, Sener M, Jackson PJ, Brindley AA. 26.  et al. 2014. Integration of energy and electron transfer processes in the photosynthetic membrane of Rhodobacter sphaeroides. Biochim. Biophys. Acta 1837:1769–80 [Google Scholar]
  27. Cassidy CK, Himes BA, Alvarez FJ, Ma J, Zhao G. 27.  et al. 2015. Cryo-electron tomography and all-atom molecular dynamics simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling. eLife 4:e08419First all-atom structure of bacteria chemosensory array revealing novel kinase conformational change. [Google Scholar]
  28. Chan KY, Gumbart J, McGreevy R, Watermeyer JM, Sewell BT, Schulten K. 28.  2011. Symmetry-restrained flexible fitting for symmetric EM maps. Structure 19:1211–18 [Google Scholar]
  29. Chandler D, Strümpfer J, Sener M, Scheuring S, Schulten K. 29.  2014. Light harvesting by lamellar chromatophores in Rhodospirillum photometricum. Biophys. J. 106:2503–10 [Google Scholar]
  30. Chapman MS.30.  1995. Restrained real-space macromolecular atomic refinement using a new resolution-dependent electron-density function. Acta Crystallogr. A 51:69–80 [Google Scholar]
  31. Chapman MS, Trzynka A, Chapman BK. 31.  2013. Atomic modeling of cryo-electron microscopy reconstructions—joint refinement of model and imaging parameters. J. Struct. Biol. 182:10–21 [Google Scholar]
  32. Chen VB, Arendall WB 3rd, Headd JJ, Keedy DA, Immormino RM. 32.  et al. 2010. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66:12–21 [Google Scholar]
  33. Cheng X, Jo S, Qi Y, Marassi FM, Im W. 33.  2015. Solid-state NMR-restrained ensemble dynamics of a membrane protein in explicit membranes. Biophys. J. 108:1954–62 [Google Scholar]
  34. Collins FS, Tabak LA. 34.  2014. NIH plans to enhance reproducibility. Nature 505:612–13 [Google Scholar]
  35. Cossio P, Hummer G. 35.  2013. Bayesian analysis of individual electron microscopy images: towards structures of dynamic and heterogeneous biomolecular assemblies. J. Struct. Biol. 184:427–37 [Google Scholar]
  36. Delarue M.36.  2008. Dealing with structural variability in molecular replacement and crystallographic refinement through normal-mode analysis. Acta Crystallogr. D 64:40–48 [Google Scholar]
  37. Diamond R.37.  1971. A real-space refinement procedure for proteins. Acta Crystallogr. A 27:436–52 [Google Scholar]
  38. Dill KA, MacCallum JL. 38.  2012. The protein-folding problem, 50 years on. Science 338:1042–46 [Google Scholar]
  39. DiMaio F, Echols N, Headd JJ, Terwilliger TC, Adams PD, Baker D. 39.  2013. Improved low-resolution crystallographic refinement with Phenix and Rosetta. Nat. Methods 10:1102–4 [Google Scholar]
  40. DiMaio F, Song Y, Li X, Brunner MJ, Xu C. 40.  et al. 2015. Atomic-accuracy models from 4.5-Å cryo-electron microscopy data with density-guided iterative local refinement. Nat. Methods 12:361–65 [Google Scholar]
  41. DiMaio F, Terwilliger TC, Read RJ, Wlodawer A, Oberdorfer G. 41.  et al. 2011. Increasing the radius of convergence of molecular replacement by density- and energy-guided protein structure optimization. Nature 473:540–43 [Google Scholar]
  42. DiMaio F, Zhang J, Chiu W, Baker D. 42.  2013. Cryo-EM model validation using independent map reconstructions. Protein Sci. 22:865–68 [Google Scholar]
  43. Dolan MA, Noah JW, Hurt D. 43.  2012. Comparison of common homology modeling algorithms: application of user-defined alignments. Methods Mol. Biol. 857:399–414 [Google Scholar]
  44. Duong F, Wickner W. 44.  1997. Distinct catalytic roles of the SecYE, SecG and SecDFyajC subunits of preprotein translocase holoenzyme. EMBO J. 16:2756–68 [Google Scholar]
  45. Eisenbach M.45.  2004. Chemotaxis London: Imperial College Press
  46. Eswar N, Webb B, Marti-Renom MA, Madhusudhan M, Eramian D. 46.  et al. 2006. Comparative protein structure modeling using Modeller. Curr. Protoc. Bioinform. 5:5–6 [Google Scholar]
  47. Falke JJ, Piasta KN. 47.  2014. Architecture and signal transduction mechanism of the bacterial chemosensory array: progress, controversies, and challenges. Curr. Opin. Struct. Biol. 29:85–94 [Google Scholar]
  48. Fenn TD, Schnieders MJ, Mustyakimov M, Wu C, Langan P. 48.  et al. 2011. Reintroducing electrostatics into macromolecular crystallographic refinement: application to neutron crystallography and DNA hydration. Structure 19:523–33 [Google Scholar]
  49. Fischer N, Neumann P, Konevega AL, Bock LV, Ficner R. 49.  et al. 2015. Structure of the E. coli ribosome-EF-Tu complex at <3 Å resolution by cs-corrected cryo-EM. Nature 520:567–70 [Google Scholar]
  50. Frank J, Agrawal RK. 50.  2000. A ratchet-like inter-subunit reorganization of the ribosome during translocation. Nature 406:318–22 [Google Scholar]
  51. Frauenfeld J, Gumbart J, van der Sluis EO, Funes S, Gartmann M. 51.  et al. 2011. Cryo-EM structure of the ribosome-SecYE complex in the membrane environment. Nat. Struct. Mol. Biol. 18:614–21 [Google Scholar]
  52. Freedman LP, Cockburn IM, Simcoe TS. 52.  2015. The economics of reproducibility in preclinical research. PLOS Biol. 13:e1002165 [Google Scholar]
  53. Freddolino PL, Harrison CB, Liu Y, Schulten K. 53.  2010. Challenges in protein folding simulations. Nat. Phys. 6:751–58 [Google Scholar]
  54. Goh BC, Perilla JR, England MR, Heyrana KJ, Craven RC, Schulten K. 54.  2015. Atomic modeling of an immature retroviral lattice using molecular dynamics and mutagenesis. Structure 23:1414–25Modeling of a critical retroviral domain whose structure could not be determined previously by experiments. [Google Scholar]
  55. Goh BC, Rynkiewicz MJ, Cafarella TR, White MR, Hartshorn KL. 55.  et al. 2013. Molecular mechanisms of inhibition of influenza by surfactant protein D revealed by large-scale molecular dynamics simulation. Biochemistry 52:8527–38 [Google Scholar]
  56. Griswold IJ, Zhou H, Matison M, Swanson RV, McIntosh LP. 56.  et al. 2002. The solution structure and interactions of CheW from Thermotoga maritima. Nat. Struct. Biol. 9:121–25 [Google Scholar]
  57. Gruner SM, Lattman EE. 57.  2015. Biostructural science inspired by next-generation X-ray sources. Annu. Rev. Biophys. 44:33–51 [Google Scholar]
  58. Haddadian EJ, Gong H, Jha AK, Yang X, DeBartolo J. 58.  et al. 2011. Automated real-space refinement of protein structures using a realistic backbone move set. Biophys. J. 101:899–909 [Google Scholar]
  59. Henderson R, Sali A, Baker ML, Carragher B, Devkota B. 59.  et al. 2012. Outcome of the first electron microscopy validation task force meeting. Structure 20:205–14 [Google Scholar]
  60. Hoffmann A, Bukau B, Kramer G. 60.  2010. Structure and function of the molecular chaperone trigger factor. Biochim. Biophys. Acta 1803:650–61 [Google Scholar]
  61. Humphrey W, Dalke A, Schulten K. 61.  1996. VMD: visual molecular dynamics. J. Mol. Graph. 14:33–38 [Google Scholar]
  62. Islam SM, Stein RA, Mchaourab HS, Roux B. 62.  2013. Structural refinement from restrained-ensemble simulations based on EPR/DEER data: application to T4 lysozyme. J. Phys. Chem. B 117:4740–54 [Google Scholar]
  63. Jiang W, Hardy D, Phillips J, MacKerell A, Schulten K, Roux B. 63.  2011. High-performance scalable molecular dynamics simulations of a polarizable force field based on classical Drude oscillators in NAMD. J. Phys. Chem. Lett. 2:87–92 [Google Scholar]
  64. Jolley CC, Wells SA, Fromme P, Thorpe MF. 64.  2008. Fitting low-resolution cryo-EM maps of proteins using constrained geometric simulations. Biophys. J. 94:1613–21 [Google Scholar]
  65. Kantardjieff KA, Rupp B. 65.  2003. Matthews coefficient probabilities: improved estimates for unit cell contents of proteins, DNA, and protein-nucleic acid complex crystals. Protein Sci. 12:1865–71 [Google Scholar]
  66. Karmali AM, Blundell TL, Furnham N. 66.  2009. Model-building strategies for low-resolution X-ray crystallographic data. Acta Crystallogr. D 65:121–27 [Google Scholar]
  67. Karplus M, Petsko GA. 67.  1990. Molecular dynamics simulations in biology. Nature 347:631–39 [Google Scholar]
  68. Kaufmann KW, Lemmon GH, DeLuca SL, Sheehan JH, Meiler J. 68.  2010. Practically useful: what the Rosetta protein modeling suite can do for you. Biochemistry 49:2987–98 [Google Scholar]
  69. Koepke J, Hu X, Muenke C, Schulten K, Michel H. 69.  1996. The crystal structure of the light-harvesting complex II (B800–850) from Rhodospirillum molischianum. Structure 4:581–97 [Google Scholar]
  70. Kol S, Nouwen N, Driessen AJM. 70.  2008. Mechanisms of YidC-mediated insertion and assembly of multimeric membrane protein complexes. J. Biol. Chem. 283:31269–73 [Google Scholar]
  71. Krishtal O.71.  2003. The ASICs: signaling molecules? Modulators?. Trends Neurosci. 26:477–83 [Google Scholar]
  72. Kucukelbir A, Sigworth FJ, Tagare HD. 72.  2014. Quantifying the local resolution of cryo-EM density maps. Nat. Methods 11:63–65 [Google Scholar]
  73. Kudryashev M, Wang RYR, Brackmann M, Scherer S, Maier T. 73.  et al. 2015. Structure of the type VI secretion system contractile sheath. Cell 160:952–62 [Google Scholar]
  74. Kumazaki K, Kishimoto T, Furukawa A, Mori H, Tanaka Y. 74.  et al. 2014. Crystal structure of Escherichia coli YidC, a membrane protein chaperone and insertase. Sci. Rep. 4:7299 [Google Scholar]
  75. Laskowski RA, MacArthur MW, Moss DS, Thornton JM. 75.  1993. PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26:283–91 [Google Scholar]
  76. Li E, Wimley WC, Hristova K. 76.  2012. Transmembrane helix dimerization: beyond the search for sequence motifs. Biochim. Biophys. Acta 1818:183–93 [Google Scholar]
  77. Li X, Mooney P, Zheng S, Booth CR, Braunfeld MB. 77.  et al. 2013. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat. Methods 10:584–90 [Google Scholar]
  78. Li X, Ortega DR, Bilwes AM, Falke JJ, Zhulin IB, Crane BR. 78.  2013. The 3.2 Å resolution structure of a receptor:CheA:CheW signaling complex defines overlapping binding sites and key residue interactions within bacterial chemosensory arrays. Biochemistry 52:3866–80 [Google Scholar]
  79. Li Y, Hu Y, Fu W, Xia B, Jin C. 79.  2007. Solution structure of the bacterial chemotaxis adaptor protein CheW from Escherichia coli. Biochem. Biophys. Res. Commun. 360:863–67 [Google Scholar]
  80. Liao M, Cao E, Julius D, Cheng Y. 80.  2013. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504:107–12 [Google Scholar]
  81. Lindert S, McCammon JA. 81.  2015. Improved cryoEM-guided iterative molecular dynamics–Rosetta protein structure refinement protocol for high precision protein structure prediction. J. Chem. Theory Comput. 11:1337–46 [Google Scholar]
  82. Lindorff-Larsen K, Piana S, Dror RO, Shaw DE. 82.  2011. How fast-folding proteins fold. Science 334:517–20 [Google Scholar]
  83. Liu C, Perilla JR, Ning J, Lu M, Hou G. 83.  et al. 2016. Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site. Nat. Commun. 7:10714 [Google Scholar]
  84. Liu J, Hu B, Morado DR, Jani S, Manson MD, Margolin W. 84.  2012. Molecular architecture of chemoreceptor arrays revealed by cryoelectron tomography of Escherichia coli minicells. PNAS 109:E1481–88 [Google Scholar]
  85. Liu Y, Sheng J, Fokine A, Meng G, Shin WH. 85.  et al. 2015. Structure and inhibition of EV-D68, a virus that causes respiratory illness in children. Science 347:71–74 [Google Scholar]
  86. Lopes PEM, Huang J, Shim J, Luo Y, Li H. 86.  et al. 2013. Polarizable force field for peptides and proteins based on the classical Drude oscillator. J. Chem. Theor. Comp. 9:5430–49 [Google Scholar]
  87. Lu M, Hou G, Zhang H, Suiter CL, Ahn J. 87.  et al. 2015. Dynamic allostery governs cyclophilin A-HIV capsid interplay. PNAS 112:14617–22 [Google Scholar]
  88. Marinelli F, Faraldo-Gómez JD. 88.  2015. Ensemble-biased metadynamics: a molecular simulation method to sample experimental distributions. Biophys. J. 108:2779–82 [Google Scholar]
  89. Marinetti GV, Cattieu K. 89.  1981. Lipid analysis of cells and chromatophores of Rhodopseudomonas sphaeroides. Chem. Phys. Lipids 28:241–51 [Google Scholar]
  90. Matthews BW.90.  1968. Solvent content of protein crystals. J. Mol. Biol. 33:491–97 [Google Scholar]
  91. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ. 91.  2007. Phaser crystallographic software. J. Appl. Crystallogr. 40:658–74 [Google Scholar]
  92. McGreevy R, Singharoy A, Li Q, Zhang J, Xu D. 92.  et al. 2014. xMDFF: molecular dynamics flexible fitting of low-resolution X-ray structures. Acta Crystallogr. D 70:2344–55Extending flexible fitting paradigms to low-resolution X-ray crystallography. [Google Scholar]
  93. McNutt M.93.  2014. Journals unite for reproducibility. Science 346:679 [Google Scholar]
  94. Melo MC, Bernardi RC, Fernandes TV, Pascutti PG. 94.  2012. GSAFold: a new application of GSA to protein structure prediction. Proteins 80:2305–10 [Google Scholar]
  95. Milazzo AC, Cheng A, Moeller A, Lyumkis D, Jacovetty E. 95.  et al. 2011. Initial evaluation of a direct detection device detector for single particle cryo-electron microscopy. J. Struct. Biol. 176:404–8 [Google Scholar]
  96. Monger T, Parson W. 96.  1977. Singlet-triplet fusion in Rhodopseudomonas sphaeroides chromatophores. A probe of the organization of the photosynthetic apparatus. Biochim. Biophys. Acta 460:393–407 [Google Scholar]
  97. Murshudov G, Skubák P, Lebedev A, Pannu N, Steiner R. 97.  et al. 2011. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D 67:355–67 [Google Scholar]
  98. Orzechowski M, Tama F. 98.  2008. Flexible fitting of high-resolution X-ray structures into cryo electron microscopy maps using biased molecular dynamics simulations. Biophys. J. 95:5692–705 [Google Scholar]
  99. Pandurangan AP, Shakeel S, Butcher SJ, Topf M. 99.  2014. Combined approaches to flexible fitting and assessment in virus capsids undergoing conformational change. J. Struct. Biol. 185:427–39 [Google Scholar]
  100. Papiz MZ, Prince SM, Howard T, Cogdell RJ, Isaacs NW. 100.  2003. The structure and thermal motion of the B800-850 LH2 complex from Rps. acidophila at 2.0 Å resolution and 100 K: new structural features and functionally relevant motions. J. Mol. Biol. 326:1523–38 [Google Scholar]
  101. Park E, Ménétret JF, Gumbart JC, Ludtke SJ, Li W. 101.  et al. 2014. Structure of the SecY channel during initiation of protein translocation. Nature 506:102–6 [Google Scholar]
  102. Park SY, Borbat PP, Gonzalez-Bonet G, Bhatnagar J, Pollard AM. 102.  et al. 2006. Reconstruction of the chemotaxis receptor-kinase assembly. Nat. Struct. Mol. Biol. 13:400–7 [Google Scholar]
  103. Perilla JR, Goh BC, Cassidy CK, Liu B, Bernardi RC. 103.  et al. 2015. Molecular dynamics simulations of large macromolecular complexes. Curr. Opin. Struct. Biol. 31:64–74 [Google Scholar]
  104. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E. 104.  et al. 2005. Scalable molecular dynamics with NAMD. J. Comp. Chem. 26:1781–802 [Google Scholar]
  105. Phillips JM, Murray PS, Murray D, Vogt VM. 105.  2008. A molecular switch required for retrovirus assembly participates in the hexagonal immature lattice. EMBO J. 27:1411–20 [Google Scholar]
  106. Ponder JW, Wu C, Ren P, Pande VS, Chodera JD. 106.  et al. 2010. Current status of the AMOEBA polarizable force field. J. Phys. Chem. B 114:2549–64 [Google Scholar]
  107. Reddy T, Shorthouse D, Parton DL, Jefferys E, Fowler PW. 107.  et al. 2015. Nothing to sneeze at: a dynamic and integrative computational model of an influenza A virion. Structure 23:584–97 [Google Scholar]
  108. Roseman AM.108.  2000. Docking structures of domains into maps from cryo-electron microscopy using local correlation. Acta Crystallogr. D 56:1332–40 [Google Scholar]
  109. Roux B, Islam SM. 109.  2013. Restrained-ensemble molecular dynamics simulations based on distance histograms from double electron-electron resonance spectroscopy. J. Phys. Chem. B 117:4733–39 [Google Scholar]
  110. Rutkowska A, Mayer MP, Hoffmann A, Merz F, Zachmann-Brand B. 110.  et al. 2008. Dynamics of trigger factor interaction with translating ribosomes. J. Biol. Chem. 283:4124–32 [Google Scholar]
  111. Scheres SHW.111.  2012. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180:519–30 [Google Scholar]
  112. Scheres SHW, Chen S. 112.  2012. Prevention of overfitting in cryo-EM structure determination. Nat. Methods 9:853–54 [Google Scholar]
  113. Scheuring S, Sturgis JN. 113.  2009. Atomic force microscopy of the bacterial photosynthetic apparatus: plain pictures of an elaborate machinery. Photosyn. Res. 102:197–211 [Google Scholar]
  114. Schlichting I, Miao J. 114.  Emerging opportunities in structural biology with X-ray free-electron lasers. Curr. Opin. Struct. Biol. 22:613–26 [Google Scholar]
  115. Schreiner E, Trabuco LG, Freddolino PL, Schulten K. 115.  2011. Stereochemical errors and their implications for molecular dynamics simulations. BMC Bioinform. 12:190 [Google Scholar]
  116. Schröder GF.116.  2015. Hybrid methods for macromolecular structure determination: experiment with expectations. Curr. Opin. Struct. Biol. 31:20–27 [Google Scholar]
  117. Schröder GF, Brunger AT, Levitt M. 117.  2007. Combining efficient conformational sampling with a deformable elastic network model facilitates structure refinement at low resolution. Structure 15:1630–41 [Google Scholar]
  118. Schröder GF, Levitt M, Brunger AT. 118.  2010. Super-resolution biomolecular crystallography with low-resolution data. Nature 464:1218–22 [Google Scholar]
  119. Schröder GF, Levitt M, Brunger AT. 119.  2014. Deformable elastic network refinement for low-resolution macromolecular crystallography. Acta Crystallogr. D 70:2241–55 [Google Scholar]
  120. Schur FKM, Dick RA, Hagen WJH, Vogt VM, Briggs JAG. 120.  2015. The structure of immature virus-like Rous sarcoma virus Gag particles reveals a structural role for the p10 domain in assembly. J. Virol. 89:10294–302 [Google Scholar]
  121. Schur FKM, Hagen WJH, Rumlová M, Ruml T, Müller B. 121.  et al. 2015. Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution. Nature 517:505–8 [Google Scholar]
  122. Schwieters CD, Kuszewski JJ, Tjandra N, Clore GM. 122.  2003. The Xplor-NIH NMR molecular structure determination package. J. Magn. Reson. 160:65–73 [Google Scholar]
  123. Seidelt B, Innis CA, Wilson DN, Gartmann M, Armache JP. 123.  et al. 2009. Structural insight into nascent polypeptide chain-mediated translational stalling. Science 326:1412–15 [Google Scholar]
  124. Sener MK, Hsin J, Trabuco LG, Villa E, Qian P. 124.  et al. 2009. Structural model and excitonic properties of the dimeric RC-LH1-PufX complex from Rhodobacter sphaeroides. Chem. Phys. 357:188–97 [Google Scholar]
  125. Shen MY, Sali A. 125.  2006. Statistical potential for assessment and prediction of protein structures. Protein Sci. 15:2507–24 [Google Scholar]
  126. Shimokawa-Chiba N, Kumazaki K, Tsukazaki T, Nureki O, Ito K, Chiba S. 126.  2015. Hydrophilic microenvironment required for the channel-independent insertase function of YidC protein. PNAS 112:5063–68 [Google Scholar]
  127. Shortle D, Simons KT, Baker D. 127.  1998. Clustering of low-energy conformations near the native structures of small proteins. PNAS 95:11158–62 [Google Scholar]
  128. Simons KT, Kooperberg C, Huang E, Baker D. 128.  1997. Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions. J. Mol. Biol. 268:209–25 [Google Scholar]
  129. Stone JE, Gullingsrud J, Grayson P, Schulten K. 129.  2001. A system for interactive molecular dynamics simulation. 2001 ACM Symposium on Interactive 3D Graphics JF Hughes, CH Séquin 191–94 New York: ACM Siggraph
  130. Stone JE, McGreevy R, Isralewitz B, Schulten K. 130.  2014. GPU-accelerated analysis and visualization of large structures solved by molecular dynamics flexible fitting. Faraday Discuss. 169:265–83 [Google Scholar]
  131. Sugita Y, Okamoto Y. 131.  1999. Replica-exchange molecular dynamics method for protein folding. Chem. Phys. Lett. 314:141–51 [Google Scholar]
  132. Tama F, Miyashita O, Brooks CL 3rd. 132.  2004. Normal mode based flexible fitting of high-resolution structure into low-resolution experimental data from cryo-EM. J. Struct. Biol. 147:315–26 [Google Scholar]
  133. Topf M, Lasker K, Webb B, Wolfson H, Chiu W, Sali A. 133.  2008. Protein structure fitting and refinement guided by cryo-EM density. Structure 16:295–307 [Google Scholar]
  134. Trabuco LG, Schreiner E, Eargle J, Cornish P, Ha T. 134.  et al. 2010. The role of L1 stalk-tRNA interaction in the ribosome elongation cycle. J. Mol. Biol. 402:741–60 [Google Scholar]
  135. Trabuco LG, Villa E, Mitra K, Frank J, Schulten K. 135.  2008. Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics. Structure 16:673–83Detailed description of the MDFF method and its application to the E. coli ribosome. [Google Scholar]
  136. Trabuco LG, Villa E, Schreiner E, Harrison CB, Schulten K. 136.  2009. Molecular dynamics flexible fitting: a practical guide to combine cryo-electron microscopy and X-ray crystallography. Methods 49:174–80 [Google Scholar]
  137. Valle M, Zavialov A, Sengupta J, Rawat U, Ehrenberg M, Frank J. 137.  2003. Locking and unlocking of ribosomal motions. Cell 114:123–34 [Google Scholar]
  138. Vashisth H, Skiniotis G, Brooks CL 3rd. 138.  2012. Using enhanced sampling and structural restraints to refine atomic structures into low-resolution electron microscopy maps. Structure 20:1453–62 [Google Scholar]
  139. Venditti V, Egner TK, Clore GM. 139.  2016. Hybrid approaches to structural characterization of conformational ensembles of complex macromolecular systems combining NMR residual dipolar couplings and solution X-ray scattering. Chem. Rev. doi: 10.1021/acs.chemrev.5b00592
  140. Villa E, Sengupta J, Trabuco LG, LeBarron J, Baxter WT. 140.  et al. 2009. Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis. PNAS 106:1063–68First application of MDFF to elucidate conformational changes of the ribosome. [Google Scholar]
  141. Wadhams GH, Armitage JP. 141.  2004. Making sense of it all: bacterial chemotaxis. Nat. Rev. Mol. Cell Biol. 5:1024–37 [Google Scholar]
  142. Waheed AA, Freed EO. 142.  2012. HIV type 1 Gag as a target for antiviral therapy. AIDS Res. Hum. Retrovir. 28:54–75 [Google Scholar]
  143. Wang RYR, Kudryashev M, Li X, Egelman EH, Basler M. 143.  et al. 2015. De novo protein structure determination from near-atomic-resolution cryo-EM maps. Nat. Methods 12:335–38Obtaining high-accuracy models using Rosetta and high-resolution cryo-EM without structural homologs. [Google Scholar]
  144. Wang X, Xu F, Liu J, Gao B, Liu Y. 144.  et al. 2013. Atomic model of rabbit hemorrhagic disease virus by cryo-electron microscopy and crystallography. PLOS Pathog. 9:e1003132 [Google Scholar]
  145. Whitford PC, Ahmed A, Yu Y, Hennelly SP, Tama F. 145.  et al. 2011. Excited states of ribosome translocation revealed through integrative molecular modeling. PNAS 108:18943–48 [Google Scholar]
  146. Wickles S, Singharoy A, Andreani J, Seemayer S, Bischoff L. 146.  et al. 2014. A structural model of the active ribosome-bound membrane protein insertase YidC. eLife 3:e03035 [Google Scholar]
  147. Wriggers W, Chacón P. 147.  2001. Modeling tricks and fitting techniques for multiresolution structures. Structure 9:779–88 [Google Scholar]
  148. Wright ER, Schooler JB, Ding HJ, Kieffer C, Fillmore C. 148.  et al. 2007. Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells. EMBO J. 26:2218–26 [Google Scholar]
  149. Wu X, Subramaniam S, Case DA, Wu KW, Brooks BR. 149.  2013. Targeted conformational search with map-restrained self-guided Langevin dynamics: application to flexible fitting into electron microscopic density maps. J. Struct. Biol. 183:429–40 [Google Scholar]
  150. Xue Y, Skrynnikov NR. 150.  2014. Ensemble MD simulations restrained via crystallographic data: Accurate structure leads to accurate dynamics. Protein Sci. 23:488–507 [Google Scholar]
  151. Yu F, Joshi SM, Ma YM, Kingston RL, Simon MN, Vogt VM. 151.  2001. Characterization of Rous sarcoma virus Gag particles assembled in vitro. J. Virol. 75:2753–64 [Google Scholar]
  152. Yusupov MM, Yusupova GZ, Baucom A, Lieberman K, Earnest TN. 152.  et al. 2001. Crystal structure of the ribosome at 5.5 Å resolution. Science 292:883–96 [Google Scholar]
  153. Yusupova GZ, Yusupov MM, Cate JHD, Noller HF. 153.  2001. The path of messenger RNA through the ribosome. Cell 106:233–41 [Google Scholar]
  154. Zhang L, Ren G. 154.  2012. IPET and FETR: experimental approach for studying molecular structure dynamics by cryo-electron tomography of a single-molecule structure. PLOS ONE 7:e30249 [Google Scholar]
  155. Zhang X, Zhang L, Tong H, Peng B, Rames MJ. 155.  et al. 2015. 3D structural fluctuation of IgG1 antibody revealed by individual particle electron tomography. Sci. Rep. 5:9803 [Google Scholar]
  156. Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B. 156.  et al. 2013. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497:643–46First all-atom model of a mature HIV capsid derived by cryo-EM and computational hybrid methods. [Google Scholar]
  157. Zhao J, Benlekbir S, Rubinstein JL. 157.  2015. Electron cryomicroscopy observation of rotational states in a eukaryotic V-ATPase. Nature 521:241–45 [Google Scholar]
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