[Binding of 1-substituted carbazolyl-3,4-dihydro-β-carbolines with DNA: Molecular dynamics simulation and MM-GBSA...

Molecular Mechanics-Generalized Born-Solvent Accessibility free energy calculations were used to analyse DNA binding affinity of 1-substituted carbazolyl-3,4-dihydro-β-carboline molecules. In this study, DNA structure with sequence of d(CGATCG)2 was used for simulations. 15 ns molecular dynamics simulations of the studied complexes were performed. The calculated free energy was compared with experimental antitumor activity (IC(50)). The predicted free energies decreased with the increase of IC(50) values. It was shown that molecules 1-6 bind to DNA via intercalation mode, while molecules 7-9 bind through groove binding mode. Also, it was found that the vdW energy term (ΔE(vdW)) and the non-polar desolvation energy (ΔG(SA)) are the favorable terms for binding energy, whereas net electrostatic energies (ΔE(ele) + ΔG(GB)) and conformational entropy energy (TΔS) are unfavorable ones.