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


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


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



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)


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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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