title: A binding mode of lambda-[tris(1,10-phenanthroline)ruthenium(II)]2+ exhibiting preference for purine-3',5'-pyrimidine sites of DNA.
abstract: Molecular mechanics calculations and molecular dynamics simulations have been used to study the binding of the partially inserted major groove complex of Lambda-[Ru(1,10-phenanthroline)3]2+ with DNA. Energy refinements of this complex showed a clear preference for binding at purine-3',5'-pyrimidine sites over pyrimidine-3',5'-purine sites. The basis for this difference is shown to be a slight change in the binding orientation induced by interchanging the purine and pyrimidine bases. This in turn provides for a better secondary interaction with the helix backbone at a point beyond the immediate binding site. It is this secondary interaction that provides the additional energetic stabilisation for complexes formed at purine-3',5'-pyrimidine sites. Molecular dynamics simulations including explicit representation of solvent support these conclusions and provide an insight into the positional stability of the ligand at a particular site. Repuckering of specific deoxyribose rings to the C3'-endo conformation seems to be an important feature of the DNA/ligand complex.
authors.affiliation: Physical Chemistry Laboratory, Oxford, England.
authors.forename: I S
authors.initials: IS
authors.lastname: Haworth
authors.forename: A H
authors.initials: AH
authors.lastname: Elcock
authors.forename: A
authors.initials: A
authors.lastname: Rodger
authors.forename: W G
authors.initials: WG
authors.lastname: Richards
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D010618:Phenanthrolines / Q000737:chemistry*; D012428:Ruthenium; D013816:Thermodynamics
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; D010618:Phenanthrolines; C034282:tris-(1,10-phenanthroline)ruthenium; D012428:Ruthenium; D004247:DNA