Effects of Trimethylamine N-Oxide (TMAO) and Crowding Agents on the Stability of RNA Hairpins

@article{citeulike:2972357, abstract = {Abstract: 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 ”Tm = Tm(¦)  Tm, where Tm(¦) and Tm are the melting temperatures at volume fraction ¦ of the osmolyte and ¦ = 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, ”Tm can vary from 5 to 15 K depending on the size of the osmolyte and the nature of RNAosmolyte 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.}, address = {Biophysics Program, Institute for Physical Science and Technology, and Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, and Department of Chemistry, Chung-Ang University, Seoul 156-756, Republic of Korea}, author = {Pincus, David L. and Hyeon, Changbong and Thirumalai, D. }, citeulike-article-id = {2972357}, doi = {10.1021/ja078326w}, journal = {J. Am. Chem. Soc.}, keywords = {nucleic\_acids, solvation}, month = {June}, number = {23}, pages = {7364--7372}, posted-at = {2008-07-08 11:59:21}, priority = {0}, title = {Effects of Trimethylamine N-Oxide (TMAO) and Crowding Agents on the Stability of RNA Hairpins}, url = {http://dx.doi.org/10.1021/ja078326w}, volume = {130}, year = {2008} }

TY - JOUR ID - citeulike:2972357 L3 - citeulike-article-id:2972357 TI - Effects of Trimethylamine N-Oxide (TMAO) and Crowding Agents on the Stability of RNA Hairpins JF - J. Am. Chem. Soc. VL - 130 IS - 23 SP - 7364 EP - 7372 AD - Biophysics Program, Institute for Physical Science and Technology, and Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, and Department of Chemistry, Chung-Ang University, Seoul 156-756, Republic of Korea N2 - Abstract: 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 ”Tm = Tm(¦)  Tm, where Tm(¦) and Tm are the melting temperatures at volume fraction ¦ of the osmolyte and ¦ = 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, ”Tm can vary from 5 to 15 K depending on the size of the osmolyte and the nature of RNAosmolyte 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. KW - nucleic_acids KW - solvation AU - Pincus, David AU - Hyeon, Changbong AU - Thirumalai, D PY - 2008/06/11/ UR - http://dx.doi.org/10.1021/ja078326w ER -