title: Molecular dynamics simulations and binding free energy analysis of DNA minor groove complexes of curcumin.
abstract: Curcumin is a natural phytochemical that exhibits a wide range of pharmacological properties, including antitumor and anticancer activities. The similarity in the shape of curcumin to DNA minor groove binding drugs is the motivation for exploring its binding affinity in the minor grooves of DNA sequences. Interactions of curcumin with DNA have not been extensively examined, while its pharmacological activities have been studied and documented in depth. Curcumin was docked with two DNA duplexes, d(GTATATAC)(2) and d(CGCGATATCGCG)(2), and molecular dynamics simulations of the complexes were performed in explicit solvent to determine the stability of the binding. In all systems, the curcumin is positioned in the minor groove in the A·T region, and was stably bound throughout the simulation, causing only minor modifications to the structural parameters of DNA. Water molecules were found to contribute to the stability of the binding of the ligand. Free energy analyses of the complexes were performed with MM-PBSA, and the binding affinities that were calculated are comparable to the values reported for other similar nucleic acid-ligand systems, indicating that curcumin is a suitable natural molecule for the development of minor groove binding drugs.
authors.affiliation: School of Pure and Applied Physics, Mahatma Gandhi University, Kottayam, Kerala 686560, India. mathewkv@gmail.com
authors.forename: Mathew Varghese
authors.initials: MV
authors.lastname: Koonammackal
authors.forename: Unnikrishnan Viswambharan Nair
authors.initials: UV
authors.lastname: Nellipparambil
authors.forename: Chellappanpillai
authors.initials: C
authors.lastname: Sudarsanakumar
mesh_terms: D003474:Curcumin / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; D004247:DNA; D003474:Curcumin