title: In Search of an Efficient Photoswitch for Functional RNA: Design Principles from a Microscopic Analysis of Azobenzene-linker-RNA Dynamics with Different Linkers.
abstract: The design of optimal photoswitches to regulate nucleic acid functionality is a considerable challenge. Azobenzene switches that are covalently bound to the nucleic acid backbone are a paradigm example that has been studied using different types of linker species connecting the chromophore to the backbone. To support experimental efforts to construct optimal azobenzene-linker-RNA combinations, we introduce here a systematic approach for theoretical analysis, which provides criteria for the local embedding of the chromophore via a chosen linker. Using a local reference frame adapted to the chromophore, quantitative measures are provided for (i) the propensity of stacking in competition with a drift toward the minor or major groove, (ii) the tendency to disrupt the native hydrogen bond network, (iii) the structural flexibility of the chromophore-linker combination, and (iv) the correlations with the presence of a base in the opposite strand. Large differences in structural stability between the trans and cis forms of the azobenzene chromophore, according to these criteria, indicate good functionality and lead to significant differences in melting temperatures. In particular, a recently synthesized deoxyribose linker proves optimal within the set of azobenzene-linker-RNA combinations considered.
authors.affiliation: Institute for Physical and Theoretical Chemistry and ‡Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt , Max-von-Laue-Straße 7, 60438 Frankfurt am Main, Germany.
authors.forename: Padmabati
authors.initials: P
authors.lastname: Mondal
authors.affiliation: Institute for Physical and Theoretical Chemistry and ‡Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt , Max-von-Laue-Straße 7, 60438 Frankfurt am Main, Germany.
authors.forename: Mithun
authors.initials: M
authors.lastname: Biswas
authors.affiliation: Institute for Physical and Theoretical Chemistry and ‡Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt , Max-von-Laue-Straße 7, 60438 Frankfurt am Main, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Goldau
authors.affiliation: Institute for Physical and Theoretical Chemistry and ‡Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt , Max-von-Laue-Straße 7, 60438 Frankfurt am Main, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Heckel
authors.affiliation: Institute for Physical and Theoretical Chemistry and ‡Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt , Max-von-Laue-Straße 7, 60438 Frankfurt am Main, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Burghardt
mesh_terms: D001391:Azo Compounds / Q000737:chemistry*; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001391:Azo Compounds; D012313:RNA; C009850:azobenzene