Structure of Rhodamine 6G-DNA Complexes from Molecular Dynamics Simulations Anela Ivanova, ² Grzegorz Jezierski, Egor Vladimirov, and Notker Ro ¨ sch* Department Chemie, Theoretische Chemie, Technische Universita ¨t Mu ¨ nchen, 85747 Garching, Germany Received May 18, 2007; Revised Manuscript Received August 6, 2007 Chromophore-DNA complexes are useful for understanding charge transport along π-stacks once their structural properties have been clarified. We studied two rhodamine 6G semicapping complexes with 15-mer B-DNA duplexes to determine the preferred orientation of the dye with respect to the neighboring base pair. For each of these systems, two distinct chromophore alignments were identified and quantified in terms of base-step parameters. The obtained geometries agree well with those derived from an NMR structure refinement of similar complexes. Cross-correlation analysis of the base-step parameters shows that slide and twist are highly interdependent during the structural transition from one conformation to the other. Introduction Structures of chromophore-DNA complexes have been intensively studied in recent years, 1-5 because such assemblies may be useful for constructing novel nanoelectronic devices. 6 Oxidized and reduced DNA can result from photoinduced electron transfer, possibly along the π-stack of the DNA helix. 7 In this process, the external chromophore acts as the electron acceptor and DNA as the electron donor or vice versa. 7-9 The best-characterized DNA modifications in terms of (mostly) electron hole transfer and its dynamics result from precise positioning of the dye through covalent bonding to one or both of the DNA strands via various linkers (bridges), mostly CH 2 tethers. 3,4,8,10,11 The rate of electron transfer was found to be highly sensitive to the sequence of the nucleobases and especially the nearest or next-nearest neighbor nucleobase. 3,4 A major factor is the electronic coupling between the chro- mophore and the nearest part of a DNA base. 3a,4a,12 For hole transfer from the chromophore, the location of the nearest guanine is important as it is the easiest one to oxidize among the canonical nucleobases. 13 Therefore, information about the mutual alignment of the chromophore and neighboring base pairs is very important. NMR spectroscopy is a powerful experimental technique for determining the structure of complex bioorganic molecules in aqueous solution. 14 From a simulation perspective, vital struc- tural information can be obtained via force-field-based molecular dynamics (MD) simulations. Also, insight into energetics and dynamics of chromophore-DNA systems can be gained at the time scale of several nanoseconds. Rhodamine 6G (R6G) is a dye frequently used as a semi- capping charge injector into DNA. 15,16 It is a zwitterionic π-conjugated molecule (Figure 1a) that contains a positively charged xanthene ring that, after excitation, can act as electron hole donor to a base of the neighboring DNA duplex. Recently, the structures of several R6G-DNA complexes have been studied by two-dimensional NMR. 16b,c Two different orientations of the dye with respect to the DNA base stack have been identified as well as a structural exchange between them on the NMR time scale. Conformational variation of rhodamine binding to DNA was also reported in other studies. 15b,17,18 Vamosi et al. were the first to publish a very detailed fluorescence study on the binding of tetramethylrhodamine via a linker to a series of DNA duplexes. 15b They discriminated three chemical species in their samples, exhibiting different patterns of interaction between rhodamine and DNA. Two of the states were fluorescent with significantly different fluorescence decay times (∼0.7 and ∼3.0 ns), and the third one was designated as a “dark state”. Later on, Unruh et al. observed three different fluorescence decay times of the same * Author to whom correspondence should be addressed. E-mail: roesch@ ch.tum.de. ² On leave from the Department of Physical Chemistry, Faculty of Chemistry, University of Sofia, 1 J. Bourchier Avenue, 1164 Sofia, Bulgaria. Figure 1. (a) Rhodamine 6G (R6G) with the aliphatic linker for binding to the DNA duplex (junction between R6G and linker indicated by a solid line). (b and c) Experimentally studied R6G-DNA complexes (NMR structure available for complex b). The dashed lines indicate the positions where the oligonucleotides were truncated to create the theoretical models R6G-CAA (modeling complex b) and R6G-GAA (modeling complex c). 3429 Biomacromolecules 2007, 8, 3429-3438 10.1021/bm700549g CCC: $37.00 © 2007 American Chemical Society Published on Web 09/26/2007