Exploration of interaction behavior between spiro[indene-2,2'-[1,3,5]oxathiazine]-1,3-diones and DNA with the help of DFT, molecular docking, and MD simulations.

A detailed computational study covering density functional theory (DFT), molecular docking, and molecular dynamics (MD) simulations of some spirocyclic compounds interacting with a B-DNA has been performed. DFT calculations were performed using the B3LYP functional with 6-311++G(d,p) basis set and were used to identify the electrophilic and nucleophilic centers in electrostatic forces. NMR results were in agreement with previous experimental data and approved the reliability of the used method and basis set. The screening results showed that spirocyclic compounds fulfill the Lipinski's rule of five and can be developed as potential oral bioavailable drug candidates. Based on molecular docking results, the binding affinities follow the < < =  <  <  <  order and ranged from -8.6 to -9.7 kcal/mol indicating a reasonably favorable interaction between DNA and investigated compounds. The adducts were stabilized by hydrophobic and hydrogen bonding interactions. The MD simulations performed for 100 ns and the results are reported in terms of variables such as root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), center of mass (COM) separation distance between DNA and ligands, intermolecular hydrogen bonds, and radial distribution functions (RDF). The MD simulations demonstrated that compounds and bind into the minor groove of 1BNA and may act as potential biological probes for B-DNA.Communicated by Ramaswamy H. Sarma.