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Monatshefte für Chemie - Chemical Monthly

, Volume 146, Issue 2, pp 389–397 | Cite as

Stabilizing non-covalent interactions of ligand aromatic moieties and proline in ligand–protein systems

  • Milena Jovanović
  • Maja Gruden-Pavlović
  • Mario ZlatovićEmail author
Original Paper

Abstract

Proline, due to its conformational specificity, is known to show some unique properties and has significant functions in the tertiary structure of proteins. It was suggested that proline could have an important influence on some vital interactions in protein as well, by engaging in non-covalent stabilization interactions with some aromatic moieties. In this work, the interactions that occur between proline and some aromatic moieties in ligands were investigated by means of the density functional theory using an exchange–correlation functional capable of taking into account dispersion interactions. The obtained results showed that the stabilization energy between a properly placed proline and an aromatic moiety could be as large as 25 kJ/mol and hence be a significant factor in placing a ligand in binding site of a protein. This indicates that the error in determining the most favorable structure of ligand–protein complexes obtained by usual molecular docking experiments sometimes could be the result of neglecting this type of interactions.

Graphical Abstract

Keywords

Ab initio calculations Non-covalent interactions Proteins Molecular modeling Density functional theory 

Notes

Acknowledgments

This research was supported by (1) the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant No. 172055) and (2) NATO’s Public Diplomacy Division in the framework of “Science for Peace” project SfP983638. The authors wish to thank Prof. Dušan Sladić for his help in preparing this manuscript.

Supplementary material

706_2014_1357_MOESM1_ESM.docx (720 kb)
Supplementary material 1 (DOCX 719 kb)

References

  1. 1.
    Greaves RB, Warwicker J (2007) BMC Struct Biol 7:18CrossRefGoogle Scholar
  2. 2.
    Nilsson IM, Sääf A, Whitley P, Gafvelin G, Waller C, von Heijne G (1998) J Mol Biol 284:1165CrossRefGoogle Scholar
  3. 3.
    Arnold S, Curtiss A, Dean DH, Alzate O (2001) FEBS Lett 490:70CrossRefGoogle Scholar
  4. 4.
    Yun RH, Anderson A, Hermans J (1991) Proteins 10:219CrossRefGoogle Scholar
  5. 5.
    Consler TG, Tsolas O, Kaback HR (1991) Biochemistry 30:1291CrossRefGoogle Scholar
  6. 6.
    Riley KE, Cui G, Merz KM Jr (2007) J Phys Chem B 111:5700CrossRefGoogle Scholar
  7. 7.
    Biedermannova L, Riley KE, Berka K, Hobza P, Vondrasek J (2008) Phys Chem Chem Phys 10:6350CrossRefGoogle Scholar
  8. 8.
  9. 9.
    Paton RS, Goodman JM (2009) J Chem Inf Model 49:944CrossRefGoogle Scholar
  10. 10.
    Jorgensen WL, Schyman P (2012) J Chem Theory Comput 8:3895CrossRefGoogle Scholar
  11. 11.
    Burnett JC, Opsenica D, Sriraghavan K, Panchal RG, Ruthel G, Hermone AR, Nguyen TL, Kenny TA, Lane DJ, McGrath CF, Schmidt JJ, Vennerstrom JL, Gussio R, Šolaja BA, Bavari S (2007) J Med Chem 50:2127CrossRefGoogle Scholar
  12. 12.
  13. 13.
    Stephens PJ, Devlin FJ, Chabalowski CF, Frisch MJ (1994) J Phys Chem 98:11623CrossRefGoogle Scholar
  14. 14.
    Wiberg KB (2004) J Comput Chem 25:1342CrossRefGoogle Scholar
  15. 15.
    Banks JL, Beard HS, Cao Y, Cho AE, Damm W, Farid R, Felts AK, Halgren TA, Mainz DT, Maple JR, Murphy R, Philipp DM, Repasky MP, Zhang LY, Berne BJ, Friesner RA, Gallicchio E, Levy RM (2005) J Comput Chem 26:1752CrossRefGoogle Scholar
  16. 16.
    Riley KE, Pitoňák M, Jurečka P, Hobza P (2010) Chem Rev 110:5023CrossRefGoogle Scholar
  17. 17.
    Chai JD, Head-Gordon M (2008) Phys Chem Chem Phys 10:6615CrossRefGoogle Scholar
  18. 18.
    Zhao Y, Truhlar DG (2008) Theor Chem Acc 120:215CrossRefGoogle Scholar
  19. 19.
    Burns LA, Vázquez-Mayagoitia A, Sumpter BG, Sherrill CD (2011) J Chem Phys 134:084107CrossRefGoogle Scholar
  20. 20.
    Du QS, Wang QY, Du LQ, Chen D, Huang RB (2013) Chem Cent J 7:92CrossRefGoogle Scholar
  21. 21.
    Gilson MK, Honig B (2004) Proteins Struct Funct. Bioinf 4:7Google Scholar
  22. 22.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery Jr JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam NJ, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ, Wallingford CT (2009) Gaussian 09, Revision A.02. Gaussian Inc., PittsburghGoogle Scholar
  23. 23.
    Jaguar, version 7.9 (2012) Schrödinger. LLC, New YorkGoogle Scholar
  24. 24.
    Maestro, version 9.3 (2012) Schrödinger. LLC, New York, NYGoogle Scholar
  25. 25.
    http://www.chemcraftprog.com. Accessed 9 Oct 2013
  26. 26.
    Boys SF, Bernardi F (1970) Mol Phys 19:553CrossRefGoogle Scholar
  27. 27.
    Epik, version 2.3 (2012) Schrödinger. LLC, New YorkGoogle Scholar
  28. 28.
    MacroModel, version 9.9 (2012) Schrödinger. LLC, New YorkGoogle Scholar
  29. 29.
    Golovin A, Henrick K (2008) BMC Bioinform 9:312CrossRefGoogle Scholar
  30. 30.
    Grimme S, Antony J, Ehrlich S, Krieg H (2010) J Chem Phys 132:154104CrossRefGoogle Scholar
  31. 31.
    Becke AD (1997) J Chem Phys 107:8554CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Milena Jovanović
    • 1
  • Maja Gruden-Pavlović
    • 1
  • Mario Zlatović
    • 1
    Email author
  1. 1.Faculty of ChemistryUniversity of BelgradeBelgradeSerbia

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