التفاصيل البيبلوغرافية
| العنوان: |
Effects of Trimethylamine N-Oxide (TMAO) and Crowding Agents on the Stability of RNA Hairpins. |
| المؤلفون: |
Pincus, David L.1, Changbong Hyeon2, Thirumalai, D.1,3 thirum@glue.umd.edu |
| المصدر: |
Journal of the American Chemical Society. 6/11/2008, Vol. 130 Issue 23, p7364-7372. 9p. 1 Diagram, 2 Charts, 7 Graphs. |
| مصطلحات موضوعية: |
*AMINES, *OXIDES, *RNA, *PHYSICAL & theoretical chemistry, *MOLECULAR dynamics |
| مستخلص: |
We study the effect of the osmolyte, Trimethylamine N-Oxide (TMAO), which accumulates in cells in response to osmotic stress, on the stability of RNA hairpins. All atom molecular dynamics (MD) simulations of a nucleotide and the 22-nucleotide RNA hairpin P5GA in an aqueous TMAO solution show that TMAO preferentially interacts with the base through the formation of a single hydrogen bond. To circumvent the difficulties of adequately sampling the conformational space of polynucleotides, we used coarse-grained models (including one that is inspired by the results of all-atom MD simulations of a single nucleotide) to probe the effects of osmoyltes on the stability of P5GA. If, as revealed by our MD simulations, the cosolute specifically interacts with only one base at a time, then we find practically no change in hairpin stability as measured by ΔTm = Tm(Φ) - Tm, where Tm(Φ) and Tm are the melting temperatures at volume fraction Φ of the osmolyte and Φ = 0, respectively. This finding is in qualitative agreement with recent experiments. If the interactions between the RNA and osmolytes are repulsive, which is appropriate for mimicking the effects of crowding, ΔTm can vary from 5 to 15 K depending on the size of the osmolyte and the nature of RNA-osmolyte interactions. Cosolutes that interact favorably with multiple bases simultaneously can stabilize the hairpin more than a crowding agent of the same size. The implications of our predictions for experiments are briefly outlined. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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