A Probabilistic Model of RNA Conformational Space

The increasing importance of non-coding RNA in biology and medicine has led to a growing interest in the problem of RNA 3-D structure prediction. As is the case for proteins, RNA 3-D structure prediction methods require two key ingredients: an accurate energy function and a conformational sampling procedure. Both are only partly solved problems. Here, we focus on the problem of conformational sampling. The current state of the art solution is based on fragment assembly methods, which construct plausible conformations by stringing together short fragments obtained from experimental structures. However, the discrete nature of the fragments necessitates the use of carefully tuned, unphysical energy functions, and their non-probabilistic nature impairs unbiased sampling. We offer a solution to the sampling problem that removes these important limitations: a probabilistic model of RNA structure that allows efficient sampling of RNA conformations in continuous space, and with associated probabilities. We show that the model captures several key features of RNA structure, such as its rotameric nature and the distribution of the helix lengths. Furthermore, the model readily generates native-like 3-D conformations for 9 out of 10 test structures, solely using coarse-grained base-pairing information. In conclusion, the method provides a theoretical and practical solution for a major bottleneck on the way to routine prediction and simulation of RNA structure and dynamics in atomic detail

Inclusion complexes of rosmarinic acid and cyclodextrins: stoichiometry, association constants, and antioxidant potential

The interaction between beta-cyclodextrin (beta-CD) and the polyphenol rosmarinic acid (RA) is here reported by H-1 NMR titration experiments. The formation of an aqueous soluble inclusion complex is confirmed and valuable information regarding mode of penetration of guest into beta-CD, stoichiometry, and stability of the complex is obtained. The analysis by the continuous variation method shows the undoubted formation of 1:1 beta-CD/RA complex. Additionally, the estimated apparent association constants reveal the importance of the asymmetry of the RA in the complexation; the incorporation of the catechol moiety closer to the carboxylic group is more favorable (K = 2,028 M-1) than from the other end of the RA molecule (K = 1,184 M-1). Finally, we have also investigated the antioxidant activity and storage stability of the beta-CD/RA complexed system; the presence of beta-CD was found to produce a remarkable enhancement on the antioxidant activity