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

eLife

Volumn 5, Issue JULY, 2016, Pages

  Singharoy, Abhishek ^a   Teo, Ivan ^a,b   McGreevy, Ryan ^a   Stone, John E ^a   Zhao, Jianhua ^c   Schulten, Klaus ^a,b  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^b University of Illinois at Urbana Champaign   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

VANILLOID RECEPTOR 1; BETA GALACTOSIDASE; TRPV1 PROTEIN, RAT; VANILLOID RECEPTOR;

ARTICLE; BIOPHYSICS; CLOUD COMPUTING; COMPUTER INTERFACE; CRYOELECTRON MICROSCOPY; MOLECULAR DYNAMICS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; THERMODYNAMICS; VALIDATION PROCESS; CHEMISTRY; IMAGE PROCESSING; PROCEDURES; ULTRASTRUCTURE;

BETA-GALACTOSIDASE; CRYOELECTRON MICROSCOPY; IMAGE PROCESSING, COMPUTER-ASSISTED; MOLECULAR DYNAMICS SIMULATION; TRPV CATION CHANNELS;

EID: 84983084125     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.16105     Document Type: Article

References (83)

1. Adams PD, Afonine PV, Bunkóczi G, Chen VB, Davis IW, Echols N, Headd JJ, Hung L-W, Kapral GJ, Grosse-Kunstleve RW, McCoy AJ, Moriarty NW, Oeffner R, Read RJ, Richardson DC, Richardson JS, Terwilliger TC, Zwart PH. 2010. PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallographica Section D Biological Crystallography 66: 213-221. doi: 10.1107/S0907444909052925
2. Afonine PV, Headd JJ, Terwilliger TC, Adams PD. 2013. New tool: Phenix.real_space_refine. Computational Crystallography Newsletter 4: 43-44.
3. Bai XC, Yan C, Yang G, Lu P, Ma D, Sun L, Zhou R, Scheres SH, Shi Y. 2015. An atomic structure of human g-secretase. Nature 525: 212-217. doi: 10.1038/nature14892
4. Barad BA, Echols N, Wang RY, Cheng Y, DiMaio F, Adams PD, Fraser JS. 2015. EMRinger: Side chain-directed model and map validation for 3D cryo-electron microscopy. Nature Methods 12: 943-946. doi: 10.1038/nmeth.3541
5. Bartesaghi A, Matthies D, Banerjee S, Merk A, Subramaniam S. 2014. Structure of b-galactosidase at 3.2-Å resolution obtained by cryo-electron microscopy. PNAS 111: 11709-11714. doi: 10.1073/pnas.1402809111
6. Bartesaghi A, Merk A, Banerjee S, Matthies D, Wu X, Milne JL, Subramaniam S. 2015. 2.2 A ° resolution cryo-EM structure of b-galactosidase in complex with a cell-permeant inhibitor. Science 348: 1147-1151. doi: 10.1126/science.aab1576
7. Best RB, Zhu X, Shim J, Lopes PE, Mittal J, Feig M, Mackerell AD. 2012. Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone j, y and side-chain c(1) and c(2) dihedral angles. Journal of Chemical Theory and Computation 8: 3257-3273. doi: 10.1021/ct300400x
8. Brown A, Shao S, Murray J, Hegde RS, Ramakrishnan V. 2015. Structural basis for stop codon recognition in eukaryotes. Nature 524: 493-496. doi: 10.1038/nature14896
9. Brunger AT, Adams PD, Fromme P, Fromme R, Levitt M, Schröder GF. 2012. Improving the accuracy of macromolecular structure refinement at 7 Å resolution. Structure 20: 957-966. doi: 10.1016/j.str.2012.04.020
10. Brünger AT. 1988. Crystallographic refinement by simulated annealing. In: Isaacs N. W, Taylor M. R (Eds). Crystallographic Computing 4: Techniques and New Technologies. Oxford: Clarendon Press. doi: 10.1016/0022-2836(88)90211-2
11. Chan KY, Gumbart J, McGreevy R, Watermeyer JM, Sewell BT, Schulten K. 2011. Symmetry-restrained flexible fitting for symmetric EM maps. Structure 19: 1211-1218. doi: 10.1016/j.str.2011.07.017
12. Chen VB, Arendall WB, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, Murray LW, Richardson JS, Richardson DC. 2010. MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallographica Section D Biological Crystallography 66: 12-21. doi: 10.1107/S0907444909042073
13. Cheng Y. 2015. Single-Particle Cryo-EM at crystallographic resolution. Cell 161: 450-457. doi: 10.1016/j.cell.2015.03.049
14. Cianfrocco MA, Leschziner AE, Scheres SH. 2015. Low cost, high performance processing of single particle cryo-electron microscopy data in the cloud. eLife 4: e06664. doi: 10.7554/eLife.06664
15. Cowtan K. 2006. The Buccaneer software for automated model building. 1. tracing protein chains. Acta Crystallographica Section D Biological Crystallography 62: 1002-1011. doi: 10.1107/S0907444906022116
16. Darnault C, Volbeda A, Kim EJ, Legrand P, Vernède X, Lindahl PA, Fontecilla-Camps JC. 2003. Ni-Zn-[Fe4-S4] and Ni-Ni-[Fe4-S4] clusters in closed and open subunits of acetyl-CoA synthase/carbon monoxide dehydrogenase. Nature Structural Biology 10: 271-279. doi: 10.1038/nsb912
17. DiMaio F, Echols N, Headd JJ, Terwilliger TC, Adams PD, Baker D. 2013. Improved low-resolution crystallographic refinement with Phenix and Rosetta. Nature Methods 10: 1102-1104. doi: 10.1038/nmeth.2648
18. DiMaio F, Song Y, Li X, Brunner MJ, Xu C, Conticello V, Egelman E, Marlovits TC, Cheng Y, Baker D. 2015. Atomic-accuracy models from 4.5-Å cryo-electron microscopy data with density-guided iterative local refinement. Nature Methods 12: 361-365. doi: 10.1038/nmeth.3286
19. Fernández JJ, Luque D, Castón JR, Carrascosa JL. 2008. Sharpening high resolution information in single particle electron cryomicroscopy. Journal of Structural Biology 164: 170-175. doi: 10.1016/j.jsb.2008.05.010
20. Fischer N, Neumann P, Konevega AL, Bock LV, Ficner R, Rodnina MV, Stark H. 2015. Structure of the E. coli ribosome-EF-Tu complex at <3 Å resolution by Cs-corrected cryo-EM. Nature 520: 567-570. doi: 10.1038/nature14275
21. Frauenfeld J, Gumbart J, Sluis EO, Funes S, Gartmann M, Beatrix B, Mielke T, Berninghausen O, Becker T, Schulten K, Beckmann R, van der Sluis EO. 2011. Cryo-EM structure of the ribosome-SecYE complex in the membrane environment. Nature Structural & Molecular Biology 18: 614-621. doi: 10.1038/nsmb.2026
22. Freddolino PL, Harrison CB, Liu Y, Schulten K. 2010. Challenges in protein-folding simulations. Nature Physics 6: 751-758. doi: 10.1038/nphys1713
23. Goh BC, Perilla JR, England MR, Heyrana KJ, Craven RC, Schulten K. 2015. Atomic modeling of an immature retroviral lattice using molecular dynamics and mutagenesis. Structure 23: 1414-1425. doi: 10.1016/j.str.2015.05.017
24. Grayson P, Tajkhorshid E, Schulten K. 2003. Mechanisms of selectivity in channels and enzymes studied with interactive molecular dynamics. Biophysical Journal 85: 36-48. doi: 10.1016/S0006-3495(03)74452-X
25. Gumbart J, Schreiner E, Trabuco LG, Chan K, Schulten K. 2011. Viewing the mechanisms of translation through the computational microscope. In: Frank J (Ed). Molecular Machines in Biology. p 142-157. doi: 10.1017/cbo9781139003704.010
26. Hsin J, Gumbart J, Trabuco LG, Villa E, Qian P, Hunter CN, Schulten K. 2009. Protein-induced membrane curvature investigated through molecular dynamics flexible fitting. Biophysical Journal 97: 321-329. doi: 10.1016/j.bpj.2009.04.031
27. Humphrey W, Dalke A, Schulten K. 1996. VMD: Visual molecular dynamics. Journal of Molecular Graphics 14: 33-38. doi: 10.1016/0263-7855(96)00018-5
28. Jiang W, Phillips JC, Huang L, Fajer M, Meng Y, Gumbart JC, Luo Y, Schulten K, Roux B. 2014. Generalized scalable multiple copy algorithms for molecular dynamics simulations in NAMD. Computer Physics Communications 185: 908-916. doi: 10.1016/j.cpc.2013.12.014
29. Jo S, Kim T, Iyer VG, Im W. 2008. CHARMM-GUI: A web-based graphical user interface for CHARMM. Journal of Computational Chemistry 29: 1859-1865. doi: 10.1002/jcc.20945
30. Jolley CC, Wells SA, Fromme P, Thorpe MF. 2008. Fitting low-resolution cryo-EM maps of proteins using constrained geometric simulations. Biophysical Journal 94: 1613-1621. doi: 10.1529/biophysj.107.115949
31. Karplus M. 1990. Molecular dynamics: Applications to proteins. In: Rivail J.-L (Ed). Modelling of Molecular Structures and Properties, Volume 71 of Studies in Physical and Theoretical Chemistry. Amsterdam: Elsevier Science Publishers. p 427-461.
32. Klauda JB, Venable RM, Freites JA, O’Connor JW, Tobias DJ, Mondragon-Ramirez C, Vorobyov I, MacKerell AD, Pastor RW. 2010. Update of the CHARMM all-atom additive force field for lipids: Validation on six lipid types. The Journal of Physical Chemistry B 114: 7830-7843. doi: 10.1021/jp101759q
33. Kovacs JA, Yeager M, Abagyan R. 2008. Damped-dynamics flexible fitting. Biophysical Journal 95: 3192-3207. doi: 10.1529/biophysj.108.132357
34. Kucukelbir A, Sigworth FJ, Tagare HD. 2014. Quantifying the local resolution of cryo-EM density maps. Nature Methods 11: 63-65. doi: 10.1038/nmeth.2727
35. Kuzmanic A, Pannu NS, Zagrovic B. 2014. X-ray refinement significantly underestimates the level of microscopic heterogeneity in biomolecular crystals. Nature Communications 5: 3220. doi: 10.1038/ncomms4220
36. Langer G, Cohen SX, Lamzin VS, Perrakis A. 2008. Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7. Nature Protocols 3: 1171-1179. doi: 10.1038/nprot.2008.91
37. Leaver-Fay A, Tyka M, Lewis SM, Lange OF, Thompson J, Jacak R, Kaufman K, Renfrew PD, Smith CA, Sheffler W, Davis IW, Cooper S, Treuille A, Mandell DJ, Richter F, Ban YE, Fleishman SJ, Corn JE, Kim DE, Lyskov S, et al. 2011. ROSETTA3: An object-oriented software suite for the simulation and design of macromolecules. Methods in Enzymology 487: 545-574. doi: 10.1016/B978-0-12-381270-4.00019-6
38. Leschziner AE, Nogales E. 2007. Visualizing flexibility at molecular resolution: Analysis of heterogeneity in single-particle electron microscopy reconstructions. Annual Review of Biophysics and Biomolecular Structure 36: 43-62. doi: 10.1146/annurev.biophys.36.040306.132742
39. Li X, Mooney P, Zheng S, Booth CR, Braunfeld MB, Gubbens S, Agard DA, Cheng Y. 2013. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nature Methods 10: 584-590. doi: 10.1038/nmeth.2472
40. Li Q, Wanderling S, Paduch M, Medovoy D, Singharoy A, McGreevy R, Villalba-Galea CA, Hulse RE, Roux B, Schulten K, Kossiakoff A, Perozo E. 2014. Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain. Nature Structural & Molecular Biology 21: 244-252. doi: 10.1038/nsmb.2768
41. Liao M, Cao E, Julius D, Cheng Y. 2013. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504: 107-112. doi: 10.1038/nature12822
42. Lindert S, McCammon JA. 2015. Improved cryoEM-guided iterative molecular dynamics-rosetta protein structure refinement protocol for high precision protein structure prediction. Journal of Chemical Theory and Computation 11: 1337-1346. doi: 10.1021/ct500995d
43. Liu C, Xiong Y. 2014. Electron density sharpening as a general technique in crystallographic studies. Journal of Molecular Biology 426: 980-993. doi: 10.1016/j.jmb.2013.11.014
44. Lopéz-Blanco JR, Chacón P. 2013. iMODFIT: Efficient and robust flexible fitting based on vibrational analysis in internal coordinates. Journal of Structural Biology 184: 261-270. doi: 10.1016/j.jsb.2013.08.010
45. Lu P, Bai XC, Ma D, Xie T, Yan C, Sun L, Yang G, Zhao Y, Zhou R, Scheres SH, Shi Y. 2014. Three-dimensional structure of human g-secretase. Nature 512: 166-170. doi: 10.1038/nature13567
46. Matthies D, Dalmas O, Borgnia MJ, Dominik PK, Merk A, Rao P, Reddy BG, Islam S, Bartesaghi A, Perozo E, Subramaniam S. 2016. Cryo-EM structures of the magnesium channel CorA reveal symmetry break upon gating. Cell 164: 747-756. doi: 10.1016/j.cell.2015.12.055
47. McGreevy R, Singharoy A, Li Q, Zhang J, Xu D, Perozo E, Schulten K. 2014. xMDFF: Molecular dynamics flexible fitting of low-resolution X-ray structures. Acta Crystallographica Section D Biological Crystallography 70: 2344-2355. doi: 10.1107/S1399004714013856
48. McGreevy R, Teo I, Singharoy A, Schulten K. 2016. Advances in the molecular dynamics flexible fitting method for cryo-EM modeling. Methods 100: 50-60. doi: 10.1016/j.ymeth.2016.01.009
49. Milazzo AC, Cheng A, Moeller A, Lyumkis D, Jacovetty E, Polukas J, Ellisman MH, Xuong NH, Carragher B, Potter CS. 2011. Initial evaluation of a direct detection device detector for single particle cryo-electron microscopy. Journal of Structural Biology 176: 404-408. doi: 10.1016/j.jsb.2011.09.002
50. Murshudov GN, Skubák P, Lebedev AA, Pannu NS, Steiner RA, Nicholls RA, Winn MD, Long F, Vagin AA. 2011. REFMAC 5 for the refinement of macromolecular crystal structures. Acta Crystallographica Section D Biological Crystallography 67: 355-367. doi: 10.1107/S0907444911001314
51. Neutze R, Brändén G, Schertler GF. 2015. Membrane protein structural biology using X-ray free electron lasers. Current Opinion in Structural Biology 33: 115-125. doi: 10.1016/j.sbi.2015.08.006
52. Noble AJ, Zhang Q, O’Donnell J, Hariri H, Bhattacharya N, Marshall AG, Stagg SM. 2013. A pseudoatomic model of the COPII cage obtained from cryo-electron microscopy and mass spectrometry. Nature Structural & Molecular Biology 20: 167-173. doi: 10.1038/nsmb.2467
53. Orzechowski M, Tama F. 2008. Flexible fitting of high-resolution x-ray structures into cryoelectron microscopy maps using biased molecular dynamics simulations. Biophysical Journal 95: 5692-5705. doi: 10.1529/biophysj.108.139451
54. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kalé L, Schulten K. 2005. Scalable molecular dynamics with NAMD. Journal of Computational Chemistry 26: 1781-1802. doi: 10.1002/jcc.20289
55. Rosenthal PB, Henderson R. 2003. Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. Journal of Molecular Biology 333: 721-745. doi: 10.1016/j.jmb.2003.07.013
56. Schröder GF, Brunger AT, Levitt M. 2007. Combining efficient conformational sampling with a deformable elastic network model facilitates structure refinement at low resolution. Structure 15: 1630-1641. doi: 10.1016/j.str.2007.09.021
57. Schröder GF, Levitt M, Brunger AT. 2010. Super-resolution biomolecular crystallography with low-resolution data. Nature 464: 1218-1222. doi: 10.1038/nature08892
58. Sener M, Hsin J, Trabuco LG, Villa E, Qian P, Hunter CN, Schulten K. 2009. Structural model and excitonic properties of the dimeric RC-LH1-PufX complex from Rhodobacter sphaeroides. Chemical Physics 357: 188-197. doi: 10.1016/j.chemphys.2009.01.003
59. Shaikh TR, Gao H, Baxter WT, Asturias FJ, Boisset N, Leith A, Frank J. 2008. SPIDER image processing for single-particle reconstruction of biological macromolecules from electron micrographs. Nature Protocols 3: 1941-1974. doi: 10.1038/nprot.2008.156
60. Singharoy A, Polavarapu A, Joshi H, Baik MH, Ortoleva P. 2013. Epitope fluctuations in the human papillomavirus are under dynamic allosteric control: A computational evaluation of a new vaccine design strategy. Journal of the American Chemical Society 135: 18458-18468. doi: 10.1021/ja407489r
61. Singharoy A, Venkatakrishnan B, Liu Y, Mayne CG, Lee S, Chen CH, Zlotnick A, Schulten K, Flood AH. 2015. Macromolecular crystallography for synthetic abiological molecules: Combining xMDFF and PHENIX for structure determination of cyanostar macrocycles. Journal of the American Chemical Society 137: 8810-8818. doi: 10.1021/jacs.5b04407
62. Stone JE, Gullingsrud J, Grayson P, Schulten K. 2001. A system for interactive molecular dynamics simulation. In: Hughes JF, Séquin CH (Eds). ACM Symposium on Interactive 3D Graphics. New York: ACM SIGGRAPH. p 191-194. doi: 10.1145/364338.364398
63. Stone JE, Phillips JC, Freddolino PL, Hardy DJ, Trabuco LG, Schulten K. 2007. Accelerating molecular modeling applications with graphics processors. Journal of Computational Chemistry 28: 2618-2640. doi: 10.1002/jcc.20829
64. Stone JE, McGreevy R, Isralewitz B, Schulten K. 2014. GPU-accelerated analysis and visualization of large structures solved by molecular dynamics flexible fitting. Faraday Discussion. 169: 265-283. doi: 10.1039/C4FD00005F
65. Sugita Y, Okamoto Y. 1999. Replica-exchange molecular dynamics method for protein folding. Chemical Physics Letters 314: 141-151. doi: 10.1016/S0009-2614(99)01123-9
66. Suhre K, Navaza J, Sanejouand Y-H. 2006. NORMA: A tool for flexible fitting of high-resolution protein structures into low-resolution electron-microscopy-derived density maps. Acta Crystallographica Section D Biological Crystallography 62: 1098-1100. doi: 10.1107/S090744490602244X
67. Tama F, Miyashita O, Brooks III CL. 2004. Normal mode based flexible fitting of high-resolution structure into low-resolution experimental data from cryo-EM. Journal of Structural Biology 147: 315-326. doi: 10.1016/j.jsb.2004.03.002
68. Tanner DE, Chan KY, Phillips JC, Schulten K. 2011. Parallel generalized born implicit solvent calculations with NAMD. Journal of Chemical Theory and Computation 7: 3635-3642. doi: 10.1021/ct200563j
69. Topf M, Baker ML, Marti-Renom MA, Chiu W, Sali A. 2006. Refinement of protein structures by iterative comparative modeling and CryoEM density fitting. Journal of Molecular Biology 357: 1655-1668. doi: 10.1016/j.jmb.2006.01.062
70. Topf M, Lasker K, Webb B, Wolfson H, Chiu W, Sali A. 2008. Protein structure fitting and refinement guided by cryo-EM density. Structure 16: 295-307. doi: 10.1016/j.str.2007.11.016
71. Trabuco LG, Villa E, Mitra K, Frank J, Schulten K. 2008. Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics. Structure 16: 673-683. doi: 10.1016/j.str.2008.03.005
72. Trabuco LG, Villa E, Schreiner E, Harrison CB, Schulten K. 2009. Molecular dynamics flexible fitting: A practical guide to combine cryo-electron microscopy and X-ray crystallography. Methods 49: 174-180. doi: 10.1016/j.ymeth.2009.04.005
73. Trabuco LG, Schreiner E, Gumbart J, Hsin J, Villa E, Schulten K. 2011. Applications of the molecular dynamics flexible fitting method. Journal of Structural Biology 173: 420-427. doi: 10.1016/j.jsb.2010.09.024
74. Unger VM. 2001. Electron cryomicroscopy methods. Current Opinion in Structural Biology 11: 548-554. doi: 10.1016/S0959-440X(00)00260-8
75. Velazquez-Muriel JA, Valle M, Santamaría-Pang A, Kakadiaris IA, Carazo JM. 2006. Flexible fitting in 3D-EM guided by the structural variability of protein superfamilies. Structure 14: 1115-1126. doi: 10.1016/j.str.2006.05.013
76. Villa E, Sengupta J, Trabuco LG, LeBarron J, Baxter WT, Shaikh TR, Grassucci RA, Nissen P, Ehrenberg M, Schulten K, Frank J. 2009. Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis. PNAS 106: 1063-1068. doi: 10.1073/pnas.0811370106
77. Wade RH. 1992. A brief look at imaging and contrast transfer. Ultramicroscopy 46: 145-156. doi: 10.1016/0304-3991(92)90011-8
78. Wickles S, Singharoy A, Andreani J, Seemayer S, Bischoff L, Berninghausen O, Soeding J, Schulten K, van der Sluis EO, Beckmann R. 2014. A structural model of the active ribosome-bound membrane protein insertase YidC. eLife 3: e03035. doi: 10.7554/eLife.03035
79. Williams L. 1983. Pyramidal parametrics. In: Proceedings of the 10th Annual Conference on Computer Graphics and Interactive Techniques. New York: ACM. p 1-11. doi: 10.1145/800059.801126
80. Wriggers W. 2010. Using situs for the integration of multi-resolution structures. Biophysical Reviews 2: 21-27. doi: 10.1007/s12551-009-0026-3
81. Wu X, Subramaniam S, Case DA, Wu KW, Brooks BR. 2013. Targeted conformational search with map-restrained self-guided Langevin dynamics: Application to flexible fitting into electron microscopic density maps. Journal of Structural Biology 183: 429-440. doi: 10.1016/j.jsb.2013.07.006
82. Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning J, Ahn J, Gronenborn AM, Schulten K, Aiken C, Zhang P. 2013. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497: 643-646. doi: 10.1038/nature12162
83. Zhao M, Wu S, Zhou Q, Vivona S, Cipriano DJ, Cheng Y, Brunger AT. 2015. Mechanistic insights into the recycling machine of the SNARE complex. Nature 518: 61-67. doi: 10.1038/nature14148