Abstract
This work is aimed at providing physical insights about the π–π 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.
Highlights
Noncovalent interactions play a unique role in biological science, control diverse phenomena including boiling points of liquids, solvation energies and determine the structures of DNA, RNA, and proteins
The results show that dispersion contributes significantly to the interaction energy (IE) is complemented by a varying degree of electrostatic interactions, where the electrostatic properties of these systems are a key determinant for their orientational preferences [10]
According to atoms in molecule (AIM) analysis, the stability can be attributed to three bond critical points (BCPs) between atoms in this conformation: (a) between the carbon of carbonyl in guanine base and one of the carbons of the indole cycle O=CÁÁÁC, (b) between one of the carbons of guanine base and intercycle nitrogen of indole HNÁÁÁC, and (c) between one of the hydrogens of NH2 group of guanine and the carbon of indole
Summary
Noncovalent interactions play a unique role in biological science, control diverse phenomena including boiling points of liquids, solvation energies and determine the structures of DNA, RNA, and proteins. Detailed suitable information of the physical factors governing this interaction will give deeper insight into the structural and functional implications of aromatic interactions in biomolecules, the nucleic acids, and to the design of new intercalating drugs with potential therapeutic value Due to their importance, there numerous studies have been performed on the stacking interactions, both experimental [22, 23] and theoretical [24, 25]. Interaction patterns exhibited by aromatic heterocycles comprise hydrophobic, polar, hydrogen bonding (H-bonding), cation-p [35], amid-p [36], halogen-p [37], and pstacking interactions [38] These heterocyclic compounds demonstrate diverse pharmacological properties, and flexibility in their structure means a high degree of differentiation that has been proven to be useful for the search of novel therapeutic agents.
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