Serverification of Molecular Modeling Applications: The Rosetta Online Server That Includes Everyone (ROSIE)

Abstract

The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code's difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step 'serverification' protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org.

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References 84

1. 1.

   Leaver-Fay A, Tyka M, Lewis SM, Lange OF, Thompson J, et al (2011 ) ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules. Methods in Enzymology 487: 545–574.

   Not in our library10.1016/b978-0-12-381270-4.00019-6

2. 2.

   Janin J (2010 ) Protein-protein docking tested in blind predictions: the CAPRI experiment. Mol Biosyst 6: 2351–2362.

   Not in our library10.1039/c005060c

3. 3.

   Chaudhury S, Lyskov S, Gray JJ (2010 ) PyRosetta: a script-based interface for implementing molecular modeling algorithms using Rosetta. Bioinformatics 26: 689–691.

   Not in our library10.1093/bioinformatics/btq007

4. 4.
   RosettaScripts: A Scripting Language Interface to the Rosetta Macromolecular Modeling Suite · 2011

   No notice
5. 5.

   Baugh EH, Lyskov S, Weitzner BD, Gray JJ (2011 ) Real-time PyMOL visualization for Rosetta and PyRosetta. PLoS ONE 6: e21931.

   Not in our library10.1371/journal.pone.0021931

6. 6.

   Eiben CB, Siegel JB, Bale JB, Cooper S, Khatib F, et al (2012 ) Increased Diels-Alderase activity through backbone remodeling guided by Foldit players. Nature biotechnology 30: 190–192.

   Not in our library10.1038/nbt.2109

7. 7.

   Jared Adolf-Bryfogle RD (2013) The PyRosetta Toolkit: A Graphical User Interface for the Rosetta Software Suite. PlosOne RosettaCon2012 collection.

   Not in our library10.1371/journal.pone.0066856

8. 8.

   Kaufmann KW, Lemmon GH, Deluca SL, Sheehan JH, Meiler J (2010 ) Practically useful: what the Rosetta protein modeling suite can do for you. Biochemistry 49: 2987–2998.

   Not in our library10.1021/bi902153g

9. 9.

   Kim DE, Chivian D, Baker D (2004 ) Protein structure prediction and analysis using the Robetta server. Nucleic Acids Research 32: W526–W531.

   Not in our library10.1093/nar/gkh468

10. 10.

    Sircar A, Kim ET, Gray JJ (2009 ) RosettaAntibody: Antibody variable region homology modeling server. Nucleic Acids Research 37: W474–W479.

    Not in our library10.1093/nar/gkp387

11. 11.

    Lyskov S, Gray JJ (2008 ) The RosettaDock server for local protein-protein docking. Nucleic Acids Res 36: W233–238.

    Not in our library10.1093/nar/gkn216

12. 12.

    London N, Schueler-Furman O (2008 ) Funnel hunting in a rough terrain: learning and discriminating native energy funnels. Structure 16: 269–279.

    Not in our library10.1016/j.str.2007.11.013

13. 13.

    London N, Schueler-Furman O (2007 ) Assessing the energy landscape of CAPRI targets by FunHunt. Proteins 69: 809–815.

    Not in our library10.1002/prot.21736

14. 14.

    London N, Raveh B, Cohen E, Fathi G, Schueler-Furman O (2011) Rosetta FlexPepDock web server–high resolution modeling of peptide–protein interactions. Nucleic Acids Research.

    Not in our library10.1093/nar/gkr431

15. 15.

    Raveh B, London N, Schueler-Furman O (2010 ) Sub-angstrom modeling of complexes between flexible peptides and globular proteins. Proteins: Structure, Function, and Bioinformatics 78: 2029–2040.

    Not in our library10.1002/prot.22716

16. 16.

    Liu Y, Kuhlman B (2006 ) RosettaDesign server for protein design. Nucleic Acids Research 34: W235–W238.

    Not in our library10.1093/nar/gkl163

17. 17.
    Benchmarking and Analysis of Protein Docking Performance in Rosetta v3.2 · 2011

    No notice
18. 18.

    Das R, Karanicolas J, Baker D (2010 ) Atomic accuracy in predicting and designing noncanonical RNA structure. Nat Meth 7: 291–294.

    Not in our library10.1038/nmeth.1433

19. 19.

    Chou FC, Sripakdeevong P, Dibrov SM, Hermann T, Das R (2013 ) Correcting pervasive errors in RNA crystallography through enumerative structure prediction. Nat Methods 10: 74–76.

    Not in our library10.1038/nmeth.2262

20. 20.

    Molski MA, Goodman JL, Chou F-C, Baker D, Das R, et al (2013 ) Remodeling a [small beta]-peptide bundle. Chemical Science 4: 319–324.

    Not in our library

21. 21.

    Bautista AD, Craig CJ, Harker EA, Schepartz A (2007 ) Sophistication of foldamer form and function in vitro and in vivo. Current Opinion in Chemical Biology 11: 685–692.

    Not in our library10.1016/j.cbpa.2007.09.009

22. 22.

    Daniels DS, Petersson EJ, Qiu JX, Schepartz A (2007 ) High-Resolution Structure of a β-Peptide Bundle. Journal of the American Chemical Society 129: 1532–1533.

    Not in our library10.1021/ja068678n

23. 23.

    Goodman JL, Petersson EJ, Daniels DS, Qiu JX, Schepartz A (2007 ) Biophysical and Structural Characterization of a Robust Octameric β-Peptide Bundle. Journal of the American Chemical Society 129: 14746–14751.

    Not in our library10.1021/ja0754002

24. 24.

    Craig CJ, Goodman JL, Schepartz A (2011 ) Enhancing β3-Peptide Bundle Stability by Design. ChemBioChem 12: 1035–1038.

    Not in our library10.1002/cbic.201000753

25. 25.

    Molski MA, Goodman JL, Craig CJ, Meng H, Kumar K, et al (2010 ) β-Peptide Bundles with Fluorous Cores. Journal of the American Chemical Society 132: 3658–3659.

    Not in our library10.1021/ja910903c

26. 26.

    Petersson EJ, Schepartz A (2008 ) Toward β-Amino Acid Proteins: Design, Synthesis, and Characterization of a Fifteen Kilodalton β-Peptide Tetramer. Journal of the American Chemical Society 130: 821–823.

    Not in our library10.1021/ja077245x

27. 27.

    Shandler SJ, Shapovalov MV, Dunbrack, Jr., DeGrado WF (2010 ) Development of a Rotamer Library for Use in β-Peptide Foldamer Computational Design. Journal of the American Chemical Society 132: 7312–7320.

    Not in our library10.1021/ja906700x

28. 28.

    Molski MA, Goodman JL, Chou F-C, Baker D, Das R, et al (2013 ) Remodeling a β-peptide bundle. Chemical Science 4: 319–324.

    Not in our library

29. 29.

    Szilágyi L (1995 ) Chemical shifts in proteins come of age. Progress in Nuclear Magnetic Resonance Spectroscopy 27: 325–442.

    Not in our library

30. 30.

    Cornilescu G, Delaglio F, Bax A (1999 ) Protein backbone angle restraints from searching a database for chemical shift and sequence homology. J Biomol NMR 13: 289–302.

    Not in our library10.1023/a:1008392405740

31. 31.

    Kuszewski J, Gronenborn AM, Clore GM (1995 ) The impact of direct refinement against proton chemical shifts on protein structure determination by NMR. J Magn Reson B 107: 293–297.

    Not in our library10.1006/jmrb.1995.1093

32. 32.

    Clore GM, Gronenborn AM (1998 ) New methods of structure refinement for macromolecular structure determination by NMR. Proc Natl Acad Sci U S A 95: 5891–5898.

    Not in our library10.1073/pnas.95.11.5891

33. 33.

    Vila JA, Aramini JM, Rossi P, Kuzin A, Su M, et al (2008 ) Quantum chemical 13C(alpha) chemical shift calculations for protein NMR structure determination, refinement, and validation. Proc Natl Acad Sci U S A 105: 14389–14394.

    Not in our library10.1073/pnas.0807105105

34. 34.

    Sripakdeevong P CM, Chang AT, Erat MC, Ziegeler M, et al. (2012) Consistent structure determination of noncanonical RNA motifs from 1H NMR chemical shift data. in preparation.

    Not in our library10.1038/nmeth.2876

35. 35.

    Das R, Baker D (2007 ) Automated de novo prediction of native-like RNA tertiary structures. Proceedings of the National Academy of Sciences 104: 14664–14669.

    Not in our library10.1073/pnas.0703836104

36. 36.

    Das R, Karanicolas J, Baker D (2010 ) Atomic accuracy in predicting and designing noncanonical RNA structure. Nat Methods 7: 291–294.

    Not in our library10.1038/nmeth.1433

37. 37.

    Almagro JC, Beavers MP, Hernandez-Guzman F, Maier J, Shaulsky J, et al (2011 ) Antibody modeling assessment. Proteins 79: 3050–3066.

    Not in our library10.1002/prot.23130

38. 38.

    Kuroda D, Shirai H, Jacobson MP, Nakamura H (2012 ) Computer-aided antibody design. Protein Eng Des Sel 25: 507–521.

    Not in our library10.1093/protein/gzs024

39. 39.

    Sivasubramanian A, Sircar A, Chaudhury S, Gray JJ (2009 ) Toward high-resolution homology modeling of antibody Fv regions and application to antibody-antigen docking. Proteins 74: 497–514.

    Not in our library10.1002/prot.22309

40. 40.

    Sircar A, Kim ET, Gray JJ (2009 ) RosettaAntibody: antibody variable region homology modeling server. Nucleic Acids Res 37: W474–479.

    Not in our library10.1093/nar/gkp387

41. 41.

    Mandell DJ, Coutsias EA, Kortemme T (2009 ) Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling. Nat Methods 6: 551–552.

    Not in our library10.1038/nmeth0809-551

42. 42.

    Kuroda D, Shirai H, Kobori M, Nakamura H (2008 ) Structural classification of CDR-H3 revisited: a lesson in antibody modeling. Proteins 73: 608–620.

    Not in our library10.1002/prot.22087

43. 43.

    Chaudhury S, Gray JJ (2008 ) Conformer selection and induced fit in flexible backbone protein-protein docking using computational and NMR ensembles. J Mol Biol 381: 1068–1087.

    Not in our library10.1016/j.jmb.2008.05.042

44. 44.
    SnugDock: Paratope Structural Optimization during Antibody-Antigen Docking Compensates for Errors in Antibody Homology Models · 2010

    No notice
45. 45.

    Fields GB, Alonso DOV, Stigter D, Dill KA (1992) Theory for the aggregation of proteins and copolymers. Journal Name: Journal of Physical Chemistry; Journal Volume: 96; Journal Issue: 10; Other Information: PBD: 14 May 1992: Medium: X; Size: pp 3974–3981.

    Not in our library

46. 46.

    Fink AL (1998 ) Protein aggregation: folding aggregates, inclusion bodies and amyloid. Fold Des 3: R9–23.

    Not in our library10.1016/s1359-0278(98)00002-9

47. 47.

    Wang W (2005 ) Protein aggregation and its inhibition in biopharmaceutics. International Journal of Pharmaceutics 289: 1–30.

    Not in our library10.1016/j.ijpharm.2004.11.014

48. 48.

    Mitraki A, King J (1989 ) Protein Folding Intermediates and Inclusion Body Formation. Nature Biotechnology 7: 690–697.

    Not in our library

49. 49.

    Heitz F, Morris MC, Divita G (2009 ) Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics. Br J Pharmacol 157: 195–206.

    Not in our library10.1111/j.1476-5381.2009.00057.x

50. 50.

    Cronican JJ, Beier KT, Davis TN, Tseng JC, Li WD, et al (2011 ) A Class of Human Proteins that Deliver Functional Proteins into Mammalian Cells In Vitro and In Vivo. Chemistry & Biology 18: 833–838.

    Not in our library10.1016/j.chembiol.2011.07.003

51. 51.

    Lund U, Rippe A, Venturoli D, Tenstad O, Grubb A, et al (2003 ) Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys. Am J Physiol Renal Physiol 284: F1226–1234.

    Not in our library10.1152/ajprenal.00316.2002

52. 52.

    Miklos AE, Kluwe C, Der BS, Pai S, Sircar A, et al (2012 ) Structure-based design of supercharged, highly thermoresistant antibodies. Chem Biol 19: 449–455.

    Not in our library10.1016/j.chembiol.2012.01.018

53. 53.

    Der BS KC, Miklos AE, Jacak R, Lyskov S, Gray JJ, Georgiou G, Ellington AD, Kuhlman B (2012) Alternative computational protocols for supercharging protein surfaces for reversible unfolding and retention of stability. in preparation.

    Not in our library10.1371/journal.pone.0064363

54. 54.

    Lawrence MS, Phillips KJ, Liu DR (2007 ) Supercharging proteins can impart unusual resilience. J Am Chem Soc 129: 10110–10112.

    Not in our library10.1021/ja071641y

55. 55.

    Mandell DJ, Kortemme T (2009 ) Computer-aided design of functional protein interactions. Nat Chem Biol 5: 797–807.

    Not in our library10.1038/nchembio.251

56. 56.

    Pokala N, Handel TM (2001 ) Review: protein design–where we were, where we are, where we’re going. J Struct Biol 134: 269–281.

    Not in our library10.1006/jsbi.2001.4349

57. 57.

    Humphris-Narayanan E, Akiva E, Varela R, S OC, Kortemme T (2012 ) Prediction of mutational tolerance in HIV-1 protease and reverse transcriptase using flexible backbone protein design. PLoS Comput Biol 8: e1002639.

    Not in our library10.1371/journal.pcbi.1002639

58. 58.

    Smith CA, Kortemme T (2010 ) Structure-Based Prediction of the Peptide Sequence Space Recognized by Natural and Synthetic PDZ Domains. Journal of Molecular Biology 402: 460–474.

    Not in our library10.1016/j.jmb.2010.07.032

59. 59.

    Treynor TP, Vizcarra CL, Nedelcu D, Mayo SL (2007 ) Computationally designed libraries of fluorescent proteins evaluated by preservation and diversity of function. Proc Natl Acad Sci U S A 104: 48–53.

    Not in our library10.1073/pnas.0609647103

60. 60.

    Smith CA, Kortemme T (2011 ) Predicting the Tolerated Sequences for Proteins and Protein Interfaces Using RosettaBackrub Flexible Backbone Design. PLoS ONE 6: e20451.

    Not in our library10.1371/journal.pone.0020451

61. 61.
    A Specificity Map for the PDZ Domain Family · 2008

    No notice
62. 62.

    Davis IW, Arendall WB, 3rd, Richardson DC, Richardson JS (2006 ) The backrub motion: how protein backbone shrugs when a sidechain dances. Structure 14: 265–274.

    Not in our library10.1016/j.str.2005.10.007

63. 63.

    Smith CA, Kortemme T (2008 ) Backrub-Like Backbone Simulation Recapitulates Natural Protein Conformational Variability and Improves Mutant Side-Chain Prediction. Journal of Molecular Biology 380: 742–756.

    Not in our library10.1016/j.jmb.2008.05.023

64. 64.

    Crooks GE, Hon G, Chandonia JM, Brenner SE (2004 ) WebLogo: a sequence logo generator. Genome Res 14: 1188–1190.

    Not in our library10.1101/gr.849004

65. 65.

    Tošovská P, Arora PS (2010 ) Oligooxopiperazines as Nonpeptidic α-Helix Mimetics. Organic Letters 12: 1588–1591.

    Not in our library10.1021/ol1003143

66. 66.

    Bullock BN, Jochim AL, Arora PS (2011 ) Assessing helical protein interfaces for inhibitor design. J Am Chem Soc 133: 14220–14223.

    Not in our library10.1021/ja206074j

67. 67.

    Patgiri A, Jochim AL, Arora PS (2008 ) A hydrogen bond surrogate approach for stabilization of short peptide sequences in alpha-helical conformation. Acc Chem Res 41: 1289–1300.

    Not in our library10.1021/ar700264k

68. 68.

    Henchey LK, Kushal S, Dubey R, Chapman RN, Olenyuk BZ, et al (2010 ) Inhibition of hypoxia inducible factor 1-transcription coactivator interaction by a hydrogen bond surrogate alpha-helix. J Am Chem Soc 132: 941–943.

    Not in our library10.1021/ja9082864

69. 69.

    Butterfoss GL, Renfrew PD, Kuhlman B, Kirshenbaum K, Bonneau R (2009 ) A preliminary survey of the peptoid folding landscape. J Am Chem Soc 131: 16798–16807.

    Not in our library10.1021/ja905267k

70. 70.

    Zuckermann RN, Kodadek T (2009 ) Peptoids as potential therapeutics. Curr Opin Mol Ther 11: 299–307.

    Not in our library

71. 71.

    Lee B, Richards FM (1971 ) The interpretation of protein structures: estimation of static accessibility. J Mol Biol 55: 379–400.

    Not in our library10.1016/0022-2836(71)90324-x

72. 72.

    Sheffler W, Baker D (2009 ) RosettaHoles: rapid assessment of protein core packing for structure prediction, refinement, design, and validation. Protein Sci 18: 229–239.

    Not in our library10.1002/pro.8

73. 73.

    Borgo B, Havranek JJ (2012 ) Automated selection of stabilizing mutations in designed and natural proteins. Proc Natl Acad Sci U S A 109: 1494–1499.

    Not in our library10.1073/pnas.1115172109

74. 74.

    Kilambi KP, Gray JJ (2012 ) Rapid calculation of protein pKa values using Rosetta. Biophys J 103: 587–595.

    Not in our library10.1016/j.bpj.2012.06.044

75. 75.

    Sripakdeevong P, Kladwang W, Das R (2011 ) An enumerative stepwise ansatz enables atomic-accuracy RNA loop modeling. Proc Natl Acad Sci U S A 108: 20573–20578.

    Not in our library10.1073/pnas.1106516108

76. 76.

    Lange OF, Baker D (2012 ) Resolution-adapted recombination of structural features significantly improves sampling in restraint-guided structure calculation. Proteins 80: 884–895.

    Not in our library10.1002/prot.23245

77. 77.

    Friedland GD, Lakomek N-A, Griesinger C, Meiler J, Kortemme T (2009 ) A Correspondence Between Solution-State Dynamics of an Individual Protein and the Sequence and Conformational Diversity of its Family. PLoS Comput Biol 5: e1000393.

    Not in our library10.1371/journal.pcbi.1000393

78. 78.

    Humphris EL, Kortemme T (2008 ) Prediction of Protein-Protein Interface Sequence Diversity Using Flexible Backbone Computational Protein Design. Structure 16: 1777–1788.

    Not in our library10.1016/j.str.2008.09.012

79. 79.

    Das R, Baker D (2007 ) Automated de novo prediction of native-like RNA tertiary structures. Proc Natl Acad Sci U S A 104: 14664–14669.

    Not in our library10.1073/pnas.0703836104

80. 80.

    Der BS, Kluwe C, Miklos AE, Jacak R, Lyskov S, et al.. (2013) Alternative computational protocols for supercharging protein surfaces for reversible unfolding and retention of stability. Submitted to PLoS One Rosetta Special Collection.

    Not in our library10.1371/journal.pone.0064363

81. 81.
    Adding diverse noncanonical backbones to rosetta: enabling peptidomimetic design. · 2013

    Not checked
82. 82.

    Kilambi Krishna P, Gray Jeffrey J (2012 ) Rapid Calculation of Protein pKa Values Using Rosetta. Biophysical journal 103: 587–595.

    Not in our library10.1016/j.bpj.2012.06.044

83. 83.

    Chaudhury S, Gray JJ (2008 ) Conformer Selection and Induced Fit in Flexible Backbone Protein–Protein Docking Using Computational and NMR Ensembles. Journal of Molecular Biology 381: 1068–1087.

    Not in our library10.1016/j.jmb.2008.05.042

84. 84.

    Lemmon G, Meiler J (2012 ) RosettaLigand Docking with Flexible XML Protocols. Methods in Molecular Biology 819: 143–155.

    Not in our library10.1007/978-1-61779-465-0_10

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