Towards understanding the interaction of (S)-thalidomide with nucleobases

Arch Biochem Biophys. 2020 Oct 30:693:108566. doi: 10.1016/j.abb.2020.108566. Epub 2020 Sep 5.

Abstract

Interaction of (S)-thalidomide molecule with four nucleobases: adenine, guanine, cytosine and thymine, is investigated in details employing density functional theory methods. Different mutual positions of the molecules are considered, with the starting geometries enabling hydrogen bond interactions between the monomers. Optimization of geometrical parameters is carried out within the B3LYP/6-311G** approximation and followed by evaluation of vibrational frequencies. Binding and interaction energies are calculated employing exchange-correlation functionals including long-range corrections and properly diffuse basis sets. The strongest interaction exists within the (S)-thalidomide-guanine complex. Interestingly, in one of the investigated (S)-thalidomide-guanine complexes two bifurcated hydrogen bonds are observed. The two hydrogens involved in one of them are bonded to a carbon atom in the α position relative to carbonyl group. The present study can be useful in the design of new anticancer and antiviral drugs interacting selectively with DNA or RNA.

Keywords: Binding energy; Density functional theory; Hydrogen bonds; Interaction energy; Nucleobases; Thalidomide.

MeSH terms

  • DNA / chemistry
  • Hydrogen Bonding
  • Nucleosides / chemistry*
  • RNA / chemistry
  • Spectrophotometry, Infrared
  • Thalidomide / chemistry*
  • Thermodynamics

Substances

  • Nucleosides
  • Thalidomide
  • RNA
  • DNA