title: Thermodynamics of binding of di- and tetrasubstituted naphthalene diimide ligands to DNA G-quadruplex.
abstract: Naphthalene diimide ligands have the potential to stabilize human telomeric G-quadruplex DNA via noncovalent interactions. Stabilization of G-quadruplex high order structures has become an important strategy to develop novel anticancer therapeutics. In this study four naphthalene diimide based ligands were analyzed in order to elucidate the principal factors determining contributions to G-quadruplex-ligand binding. Three possible modes of binding and their respective Gibbs free energies for two naphthalene diimide based di-N-alkylpyridinium substituted ligands have been determined using a molecular docking technique and compared to experimental results. The structures obtained from the molecular docking calculations, were analyzed using the ab initio based fragment molecular orbital (FMO) method in order to determine the major enthalpic contributions to the binding and types of interactions between the ligand and specific residues of the G-quadruplex. A computational methodology for the efficient and inexpensive ligand optimization as compared to fully ab initio methods based on the estimation of binding affinities of the naphthalene diimide derived ligands to G-quadruplex is proposed.
authors: Department of Chemistry and Physics, Monmouth University , 400 Cedar Avenue, West Long Branch, New Jersey 07764, United States.
authors: Gary
authors: G
authors: Prato
authors: Samantha
authors: S
authors: Silvent
authors: Sammy
authors: S
authors: Saka
authors: Massimiliano
authors: M
authors: Lamberto
authors: Dmytro
authors: D
authors: Kosenkov
mesh_terms: D005615:Freezing; D054856:G-Quadruplexes; D005740:Gases / Q000737:chemistry; D006801:Humans; D007094:Imides / Q000737:chemistry*; D008024:Ligands; D008957:Models, Genetic; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D005740:Gases; D007094:Imides; D008024:Ligands; D009281:Naphthalenes; C542131:naphthalenediimide