Molecular Biology

, Volume 50, Issue 2, pp 313–319 | Cite as

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

  • M. SargolzaeiEmail author
  • M. Afshar
  • M. N. Jorabchi
Structural and Functional Analysis of Biopolymers and Biopolymer Complexes


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 (IC50). The predicted free energies decreased with the increase of IC50 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.


anticancer drug binding affinity Gibbs free energy alkaloid 



Molecular Mechanics-Generalized Born-Solvent Accessibility


Molecular Mechanics-Molecular mechanics-Poisson Boltzmann Surface Area


Free Energy Perturbation


Thermodynamic Integration


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© Pleiades Publishing, Inc. 2016

Authors and Affiliations

  1. 1.Department of ChemistryShahrood University of TechnologyShahroodIran
  2. 2.Materials Simulation Laboratory, Department of PhysicsIran University of Science and TechnologyNarmak, TehranIran
  3. 3.Physikalische und Theoretische ChemieInstitut für Chemie, Universität RostockRostockGermany

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