A binding mode of lambda-[tris(1,10-phenanthroline)ruthenium(II)]2+ exhibiting preference for purine-3',5'-pyrimidine sites of DNA. |
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Authors: | I S Haworth A H Elcock A Rodger W G Richards |
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Institution: | Physical Chemistry Laboratory, Oxford, England. |
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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. |
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