title: A QM/MM refinement of an experimental DNA structure with metal-mediated base pairs.
abstract: A series of hybrid quantum mechanical/molecular mechanical (QM/MM) calculations was performed on models of a DNA duplex with artificial silver(I)-mediated imidazole base pairs. The optimized structures were compared to the original experimental NMR structure (Nat. Chem. 2 (2010) 229-234). The metal⋯metal distances are significantly shorter (~0.5Å) in the QM/MM model than in the original NMR structure. As a result, argentophilic interactions are feasible between the silver(I) ions of neighboring metal-mediated base pairs. Using the computationally determined metal⋯metal distances, a re-refined NMR solution structure of the DNA duplex was obtained. In this new NMR structure, all experimental constraints remain fulfilled. The new NMR structure shows less deviation from the regular B-type conformation than the original one. This investigation shows that the application of QM/MM models to generate additional constraints to be used during NMR structural refinements represents an elegant approach to obtaining high-resolution NMR structures.
authors.affiliation: Theoretical Chemistry, Organic Chemistry Institute, Westfälische Wilhelms-Universität Münster, Corrensstr. 40, 48149 Münster, Germany.
authors.forename: Sadhana
authors.initials: S
authors.lastname: Kumbhar
authors.forename: Silke
authors.initials: S
authors.lastname: Johannsen
authors.forename: Roland K O
authors.initials: RK
authors.lastname: Sigel
authors.forename: Mark P
authors.initials: MP
authors.lastname: Waller
authors.forename: Jens
authors.initials: J
authors.lastname: Müller
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry*; D008958:Models, Molecular; D011789:Quantum Theory; D012834:Silver / Q000737:chemistry*
chemical_list: D007093:Imidazoles; D012834:Silver; C029899:imidazole; D004247:DNA
keywords: DNA; Metal-mediated base pairs; Nucleobases; QM/MM