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Vol 50(2016) N 2 p. 313-319; DOI 10.1134/S0026893316020205  M. Sargolzaei1*, M. Afshar2, M.N. Jorabchi3 Binding of 1-substituted carbazolyl-3,4-dihydro-β-carbolines with DNA: Molecular dynamics simulation and MM-GBSA analysis 1Department of Chemistry, Shahrood University of Technology, Shahrood, Iran2Materials Simulation Laboratory, Department of Physics, Iran University of Science and Technology, Narmak, Tehran, 16345, Iran 3Physikalische und Theoretische Chemie, Institut für Chemie, Universität Rostock, Dr.-Lorenz-Weg 1, Rostock, 18059, Germany *Mohsen.sargolzaei@gmail.com Received - 2014-11-25; Accepted - 2015-01-26 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 (ΔEvdW) and the non-polar desolvation energy (ΔGSA) are the favorable terms for binding energy, whereas net electrostatic energies (ΔEele + ΔGGB) and conformational entropy energy (TΔS) are unfavorable ones. anticancer drug, binding affinity, Gibbs free energy, alkaloid |
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