A QM/MM refinement of an experimental DNA structure with metal-mediated base pairs.

A QM/MM refinement of an experimental DNA structure with metal-mediated base pairs.
J Inorg Biochem. 2013 Mar 28;
Authors: Kumbhar S, Johannsen S, Sigel RK, Waller MP, Müller J
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.
PMID: 23622950 [PubMed - as supplied by publisher]

Source: Journal of Inorganic Biochemistry - March 28, 2013 Category: Biochemistry Authors: Kumbhar S, Johannsen S, Sigel RK, Waller MP, Müller J Tags: J Inorg Biochem Source Type: research