Journal of Chemical Sciences

, Volume 124, Issue 1, pp 83–91 | Cite as

Bhageerath—Targeting the near impossible: Pushing the frontiers of atomic models for protein tertiary structure prediction#



Protein folding, considered to be the holy grail of molecular biology, remains intractable even after six decades since the report of the first crystal structure. Over 70,000 X-ray and NMR structures are now available in protein structural repositories and no physico-chemical solution is in sight. Molecular simulation methodologies have evolved to a stage to provide a computational solution to the tertiary structures of small proteins. Knowledge base driven methodologies are maturing in predicting the tertiary structures of query sequences which share high similarities with sequences of known structures in the databases. The void region thus seems to be medium (>100 amino acid residues) to large proteins with no sequence homologs in the databases and hence which has become a fertile ground for the genesis of hybrid models which exploit local similarities together with ab initio models to arrive at reasonable predictions. We describe here the development of Bhageerath an ab initio model and Bhageerath-H a hybrid model and present a critique on the current status of prediction of protein tertiary structures.

Graphical Abstract

Sequence to structure prediction is made using Bhageerath and Bhageerath-H method.


Ab initio protein folding molecular dynamics simulation protein structure prediction Bhageerath critical assessment of protein structure prediction (CASP) 


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  1. 1.
    Creighton T E 1990 Biochem. J. 270 1Google Scholar
  2. 2.
    Dobson C M 2003 Nature 426 884CrossRefGoogle Scholar
  3. 3.
    Editorial 2005 Science 309 78Google Scholar
  4. 4.
    Unger R and Moult J 1993 Bull. Math. Biol. 55 1183Google Scholar
  5. 5.
    Fraenkel A S 1993 Bull. Math. Biol. 55 1199Google Scholar
  6. 6.
    Baker D 2000 Nature 405 39CrossRefGoogle Scholar
  7. 7.
    Klepeis J L and Floudas C A 2004 SIAM News 37 1Google Scholar
  8. 8.
    Venkatraman J, Shankaramma S C and Balaram P 2001 Chem. Rev. 101 3131CrossRefGoogle Scholar
  9. 9.
    Lindorff-Larsen K, Piana S, Palmo K, Maragakis P, Klepeis J L, Dror R O and Shaw D E 2010 Proteins 78 1950Google Scholar
  10. 10.
    Levitt M and Warshel A 1975 Nature 253 694CrossRefGoogle Scholar
  11. 11.
    McCammon J A, Gelin B R and Karplus M 1977 Nature 267 585CrossRefGoogle Scholar
  12. 12.
    Li A and Daggett V 1995 Protein Eng. 8 1117CrossRefGoogle Scholar
  13. 13.
    Daggett V and Levitt M 1992 Proc. Natl. Acad. Sci. USA 89 5142CrossRefGoogle Scholar
  14. 14.
    Levitt M 1983 J. Mol. Biol. 168 595CrossRefGoogle Scholar
  15. 15.
    Levitt M 1983 J. Mol. Biol. 168 621CrossRefGoogle Scholar
  16. 16.
    Tirado-Rives J and Jorgensen W L 1993 Biochemistry 32 4175CrossRefGoogle Scholar
  17. 17.
    Boczko E M and Brooks C L III 1995 Science 269 393CrossRefGoogle Scholar
  18. 18.
    Demchuk E, Bashford D and Case D A 1997 Fold. Des. 2 35CrossRefGoogle Scholar
  19. 19.
    Daura X, Jaun B, Seebach D, van Gunsteren W F and Mark A E 1998 J. Mol. Biol. 280 925CrossRefGoogle Scholar
  20. 20.
    Duan Y and Kollman P A 1998 Science 282 740CrossRefGoogle Scholar
  21. 21.
    Mayor U, Johnson C M, Daggett V and Fersht A R 2000 Proc. Natl. Acad. Sci. USA 97 13518CrossRefGoogle Scholar
  22. 22.
    Zagrovic B, Sorin E J and Pande V S 2001 J. Mol. Biol. 313 151CrossRefGoogle Scholar
  23. 23.
    Simmerling C, Strockbine B and Roitberg A E 2002 J. Am. Chem. Soc. 124 11258CrossRefGoogle Scholar
  24. 24.
    Snow C D, Zagrovic B and Pande V S 2002 J. Am. Chem. Soc. 124 14548CrossRefGoogle Scholar
  25. 25.
    Freddolino P L, Liu F, Gruebele M and Schulten K 2008 Biophys. J. 94 L75CrossRefGoogle Scholar
  26. 26.
    Freddolino P L, Park S, Roux B and Schulten K 2009 Biophys. J. 96 3772CrossRefGoogle Scholar
  27. 27.
    Voelz V A, Bowman G R, Beauchamp K and Pande V S 2010 J. Am. Chem. Soc. 132 1526CrossRefGoogle Scholar
  28. 28.
    Shaw D E, Maragakis P, Lindorff-Larsen K, Piana S, Dror R O, Eastwood M P, Bank J A, Jumper J M, Salmon J K, Shan Y and Wriggers W 2010 Science 330 341CrossRefGoogle Scholar
  29. 29.
    Allen F et al. 2001 IBM Syst. J. 40 310CrossRefGoogle Scholar
  30. 30.
    Shirts M and Pande V S 2000 Science 290 1903CrossRefGoogle Scholar
  31. 31.
    Liwo A, Khalili M and Scheraga H A 2005 Proc. Natl. Acad. Sci. USA 102 2362CrossRefGoogle Scholar
  32. 32.
    Ensign D L, Kasson P M and Pande V S 2007 J. Mol. Biol. 374 806CrossRefGoogle Scholar
  33. 33.
    Cooper S, Khatib F, Treuille A, Barbero J, Lee J, Beenen M, Leaver-Fay A, Baker D, Popovic Z and Players F 2010 Nature 466 756CrossRefGoogle Scholar
  34. 34.
    Bonneau R and Baker D 2001 Annu. Rev. Biophys. Biomol. Struct. 30 173CrossRefGoogle Scholar
  35. 35.
    Petrey D and Honig B 2005 Mol. Cell 20 811CrossRefGoogle Scholar
  36. 36.
    Moult J, Pedersen J T, Judson R and Fidelis K 1995 Proteins 23 iiCrossRefGoogle Scholar
  37. 37.
    Moult J, Fidelis K, Kryshtafovych A, Rost B and Tramontano A 2009 Proteins 77 1CrossRefGoogle Scholar
  38. 38.
    Berman H M, Westbrook J, Feng Z, Gilliland G, Bhat T N, Weissig H, Shindyalov I N, Bourne P E 2000 Nucleic Acids Res. 28 235CrossRefGoogle Scholar
  39. 39.
    Floudas C A, Fung H K, McAllister S R, Monnigmann M and Rajgaria R 2006 Chem. Eng. Sci. 61 966CrossRefGoogle Scholar
  40. 40.
    Jayaram B, Bhushan K, Shenoy S R, Narang P, Bose S, Agrawal P, Sahu D and Pandey V 2006 Nucleic Acids Res. 34 6195CrossRefGoogle Scholar
  41. 41.
    Narang P, Bhushan K, Bose S and Jayaram B 2005 Phys. Chem. Chem. Phys. 7 2364CrossRefGoogle Scholar
  42. 42.
    Narang P, Bhushan K, Bose S and Jayaram B 2006 J. Biomol. Struct. Dyn. 23 385Google Scholar
  43. 43.
    Hubbard S J and Thornton J M 1993 NACCESS Computer Program (London: Department of Biochemistry and Molecular Biology, University College London)Google Scholar
  44. 44.
    Kelley L A and Sternberg M J E 2009 Nature Protocols 4 363CrossRefGoogle Scholar
  45. 45.
    Roy A, Kucukural A and Zhang Y 2010 Nature Protocols 5 725CrossRefGoogle Scholar
  46. 46.
    Zhang Y 2008 BMC Bioinformatics 9 1CrossRefGoogle Scholar
  47. 47.
    Kim D E, Chivian D and Baker D 2004 Nucleic Acids Res. 32 W526CrossRefGoogle Scholar
  48. 48.
    Soding J, Biegert A and Lupas A N 2005 Nucleic Acids Res. 33 W244CrossRefGoogle Scholar
  49. 49.

Copyright information

© Indian Academy of Sciences 2012

Authors and Affiliations

    • 1
    • 2
    • 3
    • 1
    • 2
    • 2
    • 2
  1. 1.Department of ChemistryIndian Institute of Technology DelhiNew DelhiIndia
  2. 2.Supercomputing Facility for Bioinformatics and Computational BiologyIndian Institute of Technology DelhiNew DelhiIndia
  3. 3.School of Biological SciencesIndian Institute of Technology DelhiNew DelhiIndia

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