Applied Biological Chemistry

, Volume 61, Issue 2, pp 209–226 | Cite as

An in-depth study on noncovalent stacking interactions between DNA bases and aromatic drug fragments using DFT method and AIM analysis: conformers, binding energies, and charge transfer

Article
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Abstract

This work is aimed at providing physical insights about the ππ stacking interactions of some popular drug fragments (DF) including indole (I), benzothiophene (Bt), benzofuran (Bf) and guanine (G), adenine (A), A-thymine (AT), G-cytosine (GC) base pairs using density functional theory (DFT), the atoms in molecule (AIM) theory, and natural bond orbital (NBO) analysis. Several stable conformers of present molecules and complexes were optimized at the M062X/6-311++G(d,p) level of theory. The result shows that the IG1 (see the notation below) and IA6 have maximum interaction energy in all of the two G-based and A-based conformers; and order of the adsorption strength is IG1 > BtG6 > BfG1 for G-based complexes and IA6 > BtA6 > BfG6 for A-based complexes. For the base pair–drug fragment complexes, the order of interaction energy was found according to IAT4 > BtAT3 > BfAT4 and IGC3 > BtGC2 > BfGC2, for AT and GC base pairs, respectively. Furthermore, our results show that stacking interaction leads to an increase and decrease in hydrogen bond length that involved in the nucleic base–drug fragment interactions. DFT-calculated interaction energies for all present conformers were found to be in a good agreement with the bond critical points data from AIM analysis. In contrast, no reasonable linear correlation was observed between NBO analysis and stability of the all studied conformers. Finally, in order to verify the DFT and AIM results, docking calculations were performed using AutoDock software. According to the binding energy of drug–DNA from AutoDock calculations, the D2-Bt and D1-Bf are the most and the least stable structures, respectively.

Keywords

AutoDock Binding energy Drug fragment Interaction energy ππ stacking 

Notes

Acknowledgments

Authors are very indebted to Research Committee of the University of Sistan and Baluchestan due to its authorities for financial support during the tenure of which work was completed.

Supplementary material

13765_2018_348_MOESM1_ESM.docx (258 kb)
Supplementary material 1 (DOCX 258 kb)
13765_2018_348_MOESM2_ESM.docx (34 kb)
Supplementary material 2 (DOCX 34 kb)

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Copyright information

© The Korean Society for Applied Biological Chemistry 2018

Authors and Affiliations

  1. 1.Department of Physics and Chemistry, Faculty of ScienceUniversity of NeyshaburNeyshaburIran
  2. 2.Computational Quantum Chemistry Laboratory, Department of ChemistryUniversity of Sistan and BaluchestanZahedanIran

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