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Dihedral angle preferences of amino acid residues forming various non-local interactions in proteins

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Abstract

In theory, a polypeptide chain can adopt a vast number of conformations, each corresponding to a set of backbone rotation angles. Many of these conformations are excluded due to steric overlaps. Ramachandran and coworkers were the first to look into this problem by plotting backbone dihedral angles in a two-dimensional plot. The conformational space in the Ramachandran map is further refined by considering the energetic contributions of various non-bonded interactions. Alternatively, the conformation adopted by a polypeptide chain may also be examined by investigating interactions between the residues. Since the Ramachandran map essentially focuses on local interactions (residues closer in sequence), out of interest, we have analyzed the dihedral angle preferences of residues that make non-local interactions (residues far away in sequence and closer in space) in the folded structures of proteins. The non-local interactions have been grouped into different types such as hydrogen bond, van der Waals interactions between hydrophobic groups, ion pairs (salt bridges), and ππ-stacking interactions. The results show the propensity of amino acid residues in proteins forming local and non-local interactions. Our results point to the vital role of different types of non-local interactions and their effect on dihedral angles in forming secondary and tertiary structural elements to adopt their native fold.

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References

  1. Ramachandran, G.N., Ramakrishnan, C., Sasisekharan, V.: Stereochemistry of polypeptide chain configurations. J. Mol. Biol. 7, 95–99 (1963)

    Article  Google Scholar 

  2. Ramachandran, G.N., Sasisekharan, V.: Conformation of polypeptides and proteins. Adv. Prot. Chem. 23, 283–437 (1968)

    Article  Google Scholar 

  3. Brocchieri, L., Karlin, S.: Geometry of interplanar residue contacts in protein structures. Proc. Natl. Acad. Sci. U. S. A. 91, 9297–9301 (1994)

    Article  ADS  Google Scholar 

  4. Gunasekaran, K., Ramakrishnan, C., Balaram, P.: Disallowed Ramachandran conformations of amino acid residues in protein structures. J. Mol. Biol. 264, 191–198 (1996)

    Article  Google Scholar 

  5. Walther, D., Cohen, F.E.: Conformational attractors on the Ramachandran map. Acta. Cryst. D 55, 506–517 (1999)

    Article  Google Scholar 

  6. Ho, B.K., Brasseur, R.: The Ramachandran plots of glycine and pre-proline. BMC Struct. Biol. 5, 14 (2005)

    Article  Google Scholar 

  7. Sasisekharan, V., Ponnuswamy, P.K.: Backbone and side chain conformations of amino acids and amino acid residues in peptides. Biopolymers 9, 1249–1252 (1970)

    Article  Google Scholar 

  8. Rose, G.D., Gierasch, L.M., Smith, J.A.: Turns in peptides and proteins. Adv. Prot. Chem. 37, 1–109 (1985)

    Article  Google Scholar 

  9. Venkatachalam, C.M.: Stereochemical criteria for polypeptides and proteins. V. Conformation of a system of three linked peptide units. Biopolymers 6, 1425–1436 (1968)

    Article  Google Scholar 

  10. ElKettani, M.A.E.C., Zakrzewska, K., Durup, J., Lavery, R.: An analysis of the conformational paths of citrate synthase. Proteins 16, 393–407 (1993)

    Article  Google Scholar 

  11. Vijayakumar, S., Vishveshwara, S., Ravishanker, G., Beveridge, D.L.: Differential stability of beta-sheets and alpha-helices in beta-lactamase: a high-temperature molecular dynamics study of unfolding intermediates. Biophys. J. 65, 2304–2312 (1993)

    Article  Google Scholar 

  12. Betts, M.J., Sternberg, M.J.E.: An analysis of conformational changes on protein–protein association: implications for predictive docking. Protein Eng. 12, 271–283 (1999)

    Article  Google Scholar 

  13. Hagler, A.T., Honig, B.: On the formation of protein tertiary structure on a computer. Proc. Natl. Acad. Sci. U. S. A. 75, 554–558 (1978)

    Article  ADS  Google Scholar 

  14. Neha, V.K., Ramakrishnan, C., Balaram, P.: Sparsely populated residue conformations in protein structures: revisiting experimental Ramachandran maps. Proteins 82, 1101–1112 (2014)

    Article  Google Scholar 

  15. Lakshmi, B., Sinduja, C., Archunan, G., Srinivasan, N.: Ramachandran analysis of conserved glycyl residues in homologous proteins of known structure. Protein Sci. 23, 843–850 (2014)

    Article  Google Scholar 

  16. Saravanan, K.M., Krishnaswamy, S.: Analysis of dihedral angle preferences for alanine and glycine residues in alpha and beta transmembrane regions. J. Biomol. Struct. Dyn. 33, 552–562 (2014)

    Article  Google Scholar 

  17. Tanaka, S., Scheraga, H.A.: Model of protein folding: inclusion of short, medium, and long-range interactions. Proc. Natl. Acad. Sci. U. S. A. 72, 3802–3806 (1975)

    Article  ADS  Google Scholar 

  18. Gromiha, M.M., Selvaraj, S.: Influence of medium and long range interactions in different structural classes of globular proteins. J. Biol. Phys. 23, 209–217 (1997)

    Article  Google Scholar 

  19. Gromiha, M.M., Selvaraj, S.: Importance of long-range interactions in protein folding. Biophys. Chem. 77, 49–68 (1999)

    Article  Google Scholar 

  20. Selvaraj, S., Gromiha, M.M.: Importance of long-range interactions in (α/β)8 barrel fold. J. Prot. Chem. 17, 691–697 (1998)

    Article  Google Scholar 

  21. Gromiha, M.M., Selvaraj, S.: Role of medium--and long-range interactions in discriminating globular and membrane proteins. Int. J. Biol. Macromol. 29, 25–34 (2001)

    Article  Google Scholar 

  22. Gromiha, M.M., Selvaraj, S.: Comparison between long-range interactions and contact order in determining the folding rate of two-state proteins: application of long-range order to folding rate prediction. J. Mol. Biol. 310, 27–32 (2001)

    Article  Google Scholar 

  23. Harihar, B., Selvaraj, S.: Refinement of the long-range order parameter in predicting folding rates of two-state proteins. Biopolymers 91, 928–935 (2009)

    Article  Google Scholar 

  24. Harihar, B., Selvaraj, S.: Application of long-range order to predict unfolding rates of two-state proteins. Proteins 79, 880–887 (2011)

    Article  Google Scholar 

  25. Kabsch, W., Sander, C.: On the use of sequence homologies to predict protein structure: identical pentapeptides can have completely different conformations. Proc. Natl. Acad. Sci. U. S. A. 81, 1075–1078 (1984)

    Article  ADS  Google Scholar 

  26. Minor, D.L., Kim, P.S.: Context-dependent secondary structure formation of a designed protein sequence. Nature 380, 730–734 (1996)

    Article  ADS  Google Scholar 

  27. Alexander, P.A., He, Y., Chen, Y., Orban, J., Bryan, P.N.: A minimal sequence code for switching protein structure and function. Proc. Natl. Acad. Sci. U. S. A. 106, 21149–21154 (2009)

    Article  ADS  Google Scholar 

  28. Saravanan, K.M., Balasubramanian, H., Nallusamy, S., Selvaraj, S.: Sequence and structural analysis of two designed proteins with 88% identity adopting different folds. Protein Eng. Des. Sel. 23, 911–918 (2010)

    Article  Google Scholar 

  29. Saravanan, K.M., Selvaraj, S.: Search for identical octapeptides in unrelated proteins: structural plasticity revisited. Biopolymers 98, 11–26 (2012)

    Article  Google Scholar 

  30. Pace, C.N.: Conformational stability of globular proteins. Trends Biochem. Sci. 15, 14–17 (1990)

    Article  Google Scholar 

  31. Ponnuswamy, P.K., Gromiha, M.M.: On the conformational stability of folded proteins. J. Theor. Biol. 166, 63–74 (1994)

    Article  Google Scholar 

  32. Engin, O., Sayar, M., Erman, B.: The introduction of hydrogen bond and hydrophobicity effects into the rotational isomeric states model for conformational analysis of unfolded peptides. Phys. Biol. 6, 016001 (2009)

    Article  ADS  Google Scholar 

  33. Fitzkee, N.C., Rose, G.D.: Sterics and solvation winnow accessible conformational space for unfolded proteins. J. Mol. Biol. 353, 873–887 (2005)

    Article  Google Scholar 

  34. Ohkubo, Y.Z., Brooks, C.L.: Exploring Flory’s isolated-pair hypothesis: statistical mechanics of helix-coil transitions in polyalanine and the C-peptide from RNase A. Proc. Natl. Acad. Sci. U. S. A. 100, 13916–13921 (2003)

    Article  ADS  Google Scholar 

  35. Cantor, C., Schimmel, P.: Biophysical Chemistry. WH Freeman, New York (2011)

    Google Scholar 

  36. Park, B., Levitt, M.: Energy functions that discriminate X-ray and near native folds from well-constructed decoys. J. Mol. Biol. 258, 367–392 (1996)

    Article  Google Scholar 

  37. Keskin, O., Yuret, D., Gursoy, A., Turkay, M., Erman, B.: Relationships between amino acid sequence and backbone torsion angle preferences. Proteins 55, 992–998 (2004)

    Article  Google Scholar 

  38. Porter, L.L., Rose, G.D.: Redrawing the Ramachandran plot after inclusion of hydrogen-bonding constraints. Proc. Natl. Acad. Sci. U. S. A. 108, 109–113 (2011)

    Article  ADS  Google Scholar 

  39. Thornton, J.M.: Protein Folding. WH Freeman, New York (1992)

    Google Scholar 

  40. Singh, H., Chauhan, J.S., Gromiha, M.M., Open Source Drug Discovery Consortium, Raghava, G.P.: ccPDB: compilation and creation of data sets from protein data Bank. Nucleic Acids Res. 40, D486–D489 (2012)

    Article  Google Scholar 

  41. Gromiha, M.M., Selvaraj, S.: Inter-residue interactions in protein folding and stability. Prog. Biophys. Mol. Biol. 86, 235–277 (2004)

    Article  Google Scholar 

  42. Manavalan, P., Ponnuswamy, P.K.: Hydrophobic character of amino acid residues in globular proteins. Nature 275, 673–674 (1978)

    Article  ADS  Google Scholar 

  43. Kyte, J., Doolittle, R.F.: A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157, 105–132 (1982)

    Article  Google Scholar 

  44. Tina, K.G., Bhadra, R., Srinivasan, N.: PIC: protein interactions calculator. Nucleic Acids Res. 35, W473–W476 (2007)

    Article  Google Scholar 

  45. Burley, S.K., Petsko, G.A.: Aromatic-aromatic interaction: a mechanism of protein structure stabilization. Science 229, 23–28 (1985)

    Article  ADS  Google Scholar 

  46. Overington, J.P., Johnson, M.S., Sali, A., Blundell, T.L.: Tertiary structural constraints on protein evolutionary diversity: templates, key residues and structure prediction. Proc. Roy. Soc. Biol. Sci. 241, 132–145 (1990)

    Article  ADS  Google Scholar 

  47. Munoz, V., Serrano, L.: Intrinsic secondary structure propensities of the amino acids using statistical φ,ψ matrices: comparison with experimental scales. Proteins 20, 301–311 (1994)

    Article  Google Scholar 

  48. Srinivasan, R., Rose, G.D.: LINUS: a hierarchic procedure to predict the fold of a protein. Proteins 22, 81–89 (1995)

    Article  Google Scholar 

  49. Street, A.G., Mayo, S.L.: Intrinsic β-sheet propensities result from van der Waals interactions between side chains and the local backbone. Proc. Natl. Acad. Sci. U. S. A. 96, 9074–9076 (1999)

    Article  ADS  Google Scholar 

  50. Berisio, R., Loguercio, S., De Simone, A., Zagari, A., Vitagliano, L.: Polyproline helices in protein structures: a statistical survey. Prot. Pept. Lett. 13, 847–854 (2006)

    Article  Google Scholar 

  51. Wilmot, C.M., Thornton, J.M.: β-turns and their distortions: a proposed new nomenclature. Protein Eng. 3, 479–493 (1990)

    Article  Google Scholar 

  52. Pal, D., Chakrabarti, P.: On residues in the disallowed region of the Ramachandran map. Biopolymers 63, 195–206 (2002)

    Article  Google Scholar 

  53. Bartlett, G.J., Choudhary, A., Raines, R.T., Woolfson, D.N.: N-Π interactions in proteins. Nat. Chem. Biol. 6, 615–620 (2010)

    Article  Google Scholar 

  54. Kraqelj, J., Ozenne, V., Blackledge, M., Jensen, M.R.: Conformational propensities of intrinsically disordered proteins from NMR chemical shifts. Chem. Phys. Chem. 14, 3034–3045 (2013)

    Article  Google Scholar 

  55. Jensen, M.R., Zweckstetter, M., Huang, J., Blackledge, M.: Exploring free energy landscapes of intrinsically disordered proteins at atomic resolution using NMR spectroscopy. Chem. Rev. 114, 6632–6660 (2014)

    Article  Google Scholar 

  56. Adzhubei, A.A., Sternberg, M.J., Makarov, A.A.: Polyproline II helix in proteins: structure and function. J. Mol. Biol. 425, 2100–2132 (2013)

    Article  Google Scholar 

  57. Cubellis, M.V., Caillez, F., Blundell, T.L., Lovell, S.C.: Properties of polyproline II, a secondary structure element implicated in protein-protein interactions. Proteins 58, 880–892 (2005)

    Article  Google Scholar 

  58. Makowska, J., Rodziewicz-Motowidlo, K., Makowski, M., Vila, J.A., Liwo, A., Chmurzynski, L., Scheraga, H.A.: Polyproline II conformation is one of many local conformational states and is not an overall conformation of unfolded peptides and proteins. Proc. Natl. Acad. Sci. U. S. A. 103, 1744–1749 (2006)

    Article  ADS  Google Scholar 

  59. Hagarman, A., Mathieu, D., Toal, S., Measey, T.J., Schwalbe, H., Schweitzer-Stenner, R.: Amino acids with hydrogen-bonding side chains have an intrinsic tendency to sample various turn conformations in aqueous solutions. Chemistry 17, 6789–6797 (2011)

    Article  Google Scholar 

  60. Jha, A.K., Colubri, A., Zaman, M.H., Koide, S., Sosnick, T.R., Freed, K.F.: Helix, sheet and polyproline II frequencies and strong nearest neighbor effects in a restricted coil library. Biochemistry 44, 9691–9702 (2005)

    Article  Google Scholar 

  61. Toal, S., Schweitzer-Stenner, R.: Local order in the unfolded state: conformational biases and nearest neighbor interactions. Biomolecules 4, 725–773 (2014)

    Article  Google Scholar 

  62. Swindells, M.B., MacArthur, M.W., Thornton, J.M.: Intrinsic phi, psi propensities of amino acids, derived from the coil regions of known structures. Nat. Struct. Biol. 2, 596–603 (1995)

    Article  Google Scholar 

  63. Thornton, J.M., Jones, D., MacArthur, M., Orengo, C., Swindells, M.: Protein folds: towards understanding folding from inspection of native structures. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 348, 71–79 (1995)

    Article  ADS  Google Scholar 

  64. Bellesia, G., Jewett, A.I., Shea, J.E.: Sequence periodicity and secondary structure propensity in model proteins. Protein Sci. 19, 141–154 (2010)

    Article  Google Scholar 

  65. Munoz, V., Seranno, L.: Local versus nonlocal interactions in protein folding and stability – an experimentalist’s point of view. Fold. Des. 1, 71–77 (1996)

    Article  Google Scholar 

  66. Thukral, L., Shenoy, S.R., Bhushan, K., Jayaram, B.: ProRegIn: a regularity index for the selection of native-like tertiary structures of proteins. J. Biosci. 32, 71–81 (2007)

    Article  Google Scholar 

  67. Ponnuraj, K., Saravanan, K.M.: Dihedral angle preferences of DNA and RNA binding amino acid residues in proteins. Int. J. Biol. Macromol. 97, 434–439 (2017)

    Article  Google Scholar 

  68. Zaman, M.H., Shen, M.Y., Berry, R.S., Freed, K.F., Sosnick, T.R.: Investigations into sequence and conformational dependence of backbone entropy, inter chain dynamics and the Flory isolated-pair hypothesis for peptides. J. Mol. Biol. 331, 693–711 (2003)

    Article  Google Scholar 

  69. Ting, D., Wang, G., Shapovalov, M., Mitra, R., Jordan, M.I., Dunbrack Jr., R.L.: Neighbor-dependent Ramachandran probability distributions of amino acids developed from a hierarchical Dirichlet process model. PLoS Comput. Biol. 6, e1000763 (2010)

    Article  ADS  MathSciNet  Google Scholar 

  70. Espinoza-Fonseca, L.M., Llizalitturi-Flores, I., Correa-Basurto, J.: Backbone conformational preferences of an intrinsically disordered protein in solution. Mol. BioSyst. 8, 1798–1805 (2012)

    Article  Google Scholar 

  71. Schwalbe, M., Ozenne, V., Bibow, S., Jaremko, M., Jaremko, L., Gajda, M., Jensen, M.R., Biernat, J., Becker, S., Mandelkow, E., Zweckstetter, M., Blackledge, M.: Predictive atomic resolution descriptions of intrinsically disordered hTau40 and α-synuclein in solution from NMR and small angle scattering. Structure. 22, 238–249 (2014)

    Article  Google Scholar 

  72. Schweitzer-Stenner, R., Toal, S.E.: Construction and comparison of the statistical coil states of unfolded and intrinsically disordered proteins from nearest neighbor corrected conformational propensities of short peptides. Mol. BioSyst. 12, 3294 (2016)

    Article  Google Scholar 

  73. Kauzmann, W.: Some factors in the interpretation of protein denaturation. Adv. Protein Chem. 14, 1–63 (1959)

    Article  Google Scholar 

  74. Thomas, P.D., Dill, K.A.: Local and nonlocal interactions in globular proteins and mechanisms of alcohol denaturation. Protein Sci. 2, 2050–2065 (1993)

    Article  Google Scholar 

  75. Dill, K.A., Truskett, T.M., Vlachy, V., Hribar-Lee, B.: Modeling water, the hydrophobic effect, and ion salvation. Ann. Rev. Biophys. Biomol. Struct. 34, 173–199 (2005)

    Article  Google Scholar 

  76. Dasgupta, D., Kaushik, R., Jayaram, B.: From Ramachandran maps to tertiary structures of proteins. J. Phys. Chem. B 119, 11136–11145 (2015)

    Article  Google Scholar 

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Acknowledgments

We thank the anonymous reviewers for constructive comments. KMS is supported by a National Post-Doctoral Fellowship (File No: PDF/2015/000276) by Science Engineering Research Board (SERB), Government of India under the mentorship of Prof. P. Karthe at University of Madras. SS thanks UGC for the award of Emeritus Fellowship (Grant No: F.6-6/2014-15/EMERITUS-2014-15-GEN-4545/(SA-II)).

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  1. Centre of Advanced Study in Crystallography & Biophysics, University of Madras, Guindy Campus, Chennai, Tamil Nadu, 600 025, India

    Konda Mani Saravanan & Samuel Selvaraj

  2. Department of Bioinformatics, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620024, India

    Samuel Selvaraj

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  1. Konda Mani Saravanan
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Saravanan, K.M., Selvaraj, S. Dihedral angle preferences of amino acid residues forming various non-local interactions in proteins. J Biol Phys 43, 265–278 (2017). https://doi.org/10.1007/s10867-017-9451-x

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