Journal of Biomolecular Structure and Dynamics
ISSN: 0739-1102 (Print) 1538-0254 (Online) Journal homepage: http://www.tandfonline.com/loi/tbsd20
8 Using pseudorotation as a reaction coordinate in free energy simulations of nucleic acids Li Li & Jack W. Szostak To cite this article: Li Li & Jack W. Szostak (2013) 8 Using pseudorotation as a reaction coordinate in free energy simulations of nucleic acids, Journal of Biomolecular Structure and Dynamics, 31:sup1, 5-5, DOI: 10.1080/07391102.2013.786334 To link to this article: http://dx.doi.org/10.1080/07391102.2013.786334
Published online: 29 May 2013.
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Date: 21 November 2016, At: 04:43
Book of Abstracts. Albany 2013: The 18th Conversation References Engelhart, A. E., Powner, M. P., & Szostak, J. W. (in press). Functional RNAs exhibit tolerance for non-heritable 2′-5′ vs. 3′-5′ backbone heterogeneity. Nature Chemistry. Trevino, S. G., Zhang, N., Elenko, M. P., Luptak, A., & Szostak, J. W. (2011). Evolution of functional nucleic acids in the presence of nonheritable backbone heterogeneity. Proceedings of National Academy of Science of USA, 108, 13492–13497.
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Using pseudorotation as a reaction coordinate in free energy simulations of nucleic acids
Li Li and Jack W. Szostak* Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114 *Email:
[email protected], Phone: (617) 726-5980, Fax: (617) 643-3328
Backbone sugar groups are central components of nucleic acids. The conformations of the ribose/deoxyribose can be elegantly described using the concept of pseudorotation (Altona and Sundaralingam, 1972), and are dominated by the C2′- and C3′-endo conformers. The free energy barrier of the transition between these two major puckering modes can be probed by NMR relaxation experiments (Johnson and Hoogstraten, 2008), but an atomic picture of the transition path per se is only available for several truncated nucleoside analogues (Brameld & Goddard III, 1999). Here, we implemented a new free energy simulation method for Molecular Dynamics simulations using pseudorotation as the reaction coordinate (Cremer and Pople, 1975). This allowed us to compute the free energy landscape of a complete pseudorotation cycle. The free energy landscape revealed not only the relative stability of C2′- and C3′-endo conformers, but also the main transition path and its free energy barrier. As a validation of our new approach, we calculated free energy surface of the pseudorotation of guanosine monophosphate. The free energy surface revealed that the C2′-endo conformation is 1 kcal/mol that is more stable and the free energy barrier for the transition is 4.5–5 kcal/mol. These are in excellent agreement with previous NMR measurements (Zhang et al., 2012; Röder et al., 1975). We have further applied this method to other systems that are important in pre-biotic chemistry, including an RNA duplex with unique 2′, 5′phosphodiester linkages. This research is supported by the Howard Hughes Medical Institute. References Altona, C., & Sundaralingam, M. (1972). Journal of the American Chemical Society, 94, 8205–8212.
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Brameld, K. A., & Goddard III, W. A. (1999). Journal of the American Chemical Society, 121, 985–993. Cremer, D., & Pople, J. (1975). A. Journal of the American Chemical Society, 97, 1354–1358. Johnson, J. E., & Hoogstraten, C. G. (2008). Journal of the American Chemical Society, 130, 16757–16769. Röder, O., Lüdemann, H.-D., & von Goldammer, E. (1975). European Journal of Biochemistry, 53, 517–524. Zhang, N., Zhang, S., & Szostak, J. W. (2012). Journal of the American Chemical Society, 134, 3691–3694.
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Prebiotic RNA synthesis: significance of mineral salts in montmorillonitecatalyzed reactions
Prakash C. Joshi*, Michael F. Aldersley and James P. Ferris The New York Center for Astrobiology and Department of Chemistry & Chemical Biology, RPI, Troy, NY 12180 *Email:
[email protected], Phone: (518) 276-8494, Fax: (518) 276-4887
The dual properties of RNA as an enzyme catalyst and its ability to store genetic information suggest that early life was based on RNA, and DNA and protein evolved from it. Our lab has demonstrated synthesis of long RNA oligomers by Na+-montmorillonite-catalyzed reactions of 5′-end-activated mononucleotides (Joshi et al., 2009). The Na+-montmorillonite not only catalyzes the prebiotic synthesis of RNA but also facilitates homochiral selection (Joshi et al., 2011, 2013). The montmorillonite-catalyzed reactions of 5′-phosphorimidazolide of adenosine were further investigated to study the effect of salts. These reactions were found to be dependent on the nature of mineral salts present. While montmorillonite (pH 7) produced only dimers in water, addition of sodium chloride (1 M) enhanced the chain length of oligomers to 10-mers as detected by HPLC. Magnesium chloride produced a similar effect but the presence of both sodium chloride and magnesium chloride did not produce any difference in the oligomer chain length. The effect of monovalant cations in RNA synthesis was of the following order: Li+ > Na+ > K+. A similar effect was observed with the anions, enhancing catalysis in the following order: Cl > Br > I . Inorganic salts that tend to salt out organic compounds from water and salts which show salt-in effects had no effect in the oligomerization process, indicating that the montmorillonite-catalyzed RNA synthesis is not affected by hydrophobic or hydrophilic interactions. A 2.3-fold decrease in the yield of cyclic dimer was observed upon increasing the sodium chloride concentration from 0.2 M to 2.0 M. Inhibition of cyclic dimer formation is essential for increasing the yield of linear dimers as well as the overall chain length. The results of this study show that the presence of salts is essential in prebiotic RNA synthesis catalyzed by clay minerals.
