title: [Binding of 1-substituted carbazolyl-3,4-dihydro-β-carbolines with DNA: Molecular dynamics simulation and MM-GBSA analysis].
abstract: 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.
authors.affiliation: Department of Chemistry, Shahrood University of Technology, Shahrood, Iran.|Mohsen.sargolzaei@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Sargolzaei
authors.affiliation: Materials Simulation Laboratory, Department of Physics, Iran University of Science and Technology, Narmak, Tehran, 16345, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Afshar
authors.affiliation: Physikalische und Theoretische Chemie, Institut für Chemie, Universität Rostock, Dr.-Lorenz-Weg 1, Rostock, 18059, Germany.
authors.forename: M N
authors.initials: MN
authors.lastname: Jorabchi
mesh_terms: D002243:Carbolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004734:Energy Metabolism; D056004:Molecular Dynamics Simulation; D013816:Thermodynamics
chemical_list: D002243:Carbolines; D004247:DNA
keywords: Gibbs free energy; alkaloid; anticancer drug; binding affinity