A model for the stabilities of RNA hairpins based on a study of the sequence dependence of stability for hairpins of six nucleotides

Abstract

Thermodynamic parameters are reported for hairpin formation in 1 M NaCl by RNA sequences of the type GGCXUAAUYGCC, where XY is the set of 10 possible mismatch base pairs. A nearest neighbor analysis of the data indicates the free energy for loop formation at 37 C varies from 2.9 to 4.5 kcal/mol. Thermodynamic parameters are also reported for hairpin formation by RNA sequences of the type GGXGUAAUAYCC (where XY are CG, GC, AU, UA, GU, and UG), with the common naturally occurring GA first mismatch (45% of small and large subunit rRNA loops of six). These results allow the development of a model to predict the stability of RNA hairpin loops. The model includes the size of the loop, the identity of the closing base pair, the free energy increment (delta G zero 37MM) for interaction of the closing base pair with the first mismatch, and an additional stabilization term for GA and UU first mismatches. delta G zero 37L(n) = delta G zero 37i(n) + delta G zero 37MM + 0.4 (if closed by AU or UA) -0.7 (if first mismatch is GA or UU). Here delta G zero 37i(n) is the free energy for initiating a loop of n nucleotides. delta G zero 37i(n) for n = 4-9 is 4.9, 4.4, 5.0, 5.0, 5.1, and 5.2 kcal/mol, respectively. The delta G zero 37MM is derived from measurements of model duplexes with terminal mismatches. The model gives good agreement when tested against four naturally occurring hairpin sequences.

Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure

“…Thermodynamic parameters are based on the set of Xia et al (44)(45)(46) and Mathews et al (8). Hairpin loop parameters (Tables 1 and 2) are revised on the basis of recent experimental results (47,48) and the previous database of RNA hairpin stabilities (49)(50)(51)(52)(53)(54)(55).…”

Computational approaches for RNA energy parameter estimation

“…Secondly, we collected a thermodynamic set denoted by T-Full that contains data from 1291 optical melting experiments, published in 53 research articles Sugimoto et al 1986Sugimoto et al , 1987Uhlenbeck 1988, 1989;Longfellow et al 1990;SantaLucia et al 1990SantaLucia et al , 1991aAntao et al 1991;He et al 1991;Peritz et al 1991;Antao and Tinoco 1992;Serra et al 1993Serra et al , 1994Serra et al , 1997Serra et al , 2004Walter et al 1994;Morse and Draper 1995;Wu et al 1995;Laing and Hall 1996;McDowell and Turner 1996;McDowell et al 1997;Schroeder et al 1996Schroeder et al , 2003Xia et al 1997Xia et al , 1998Giese et al 1998;Kierzek et al 1999;Meroueh and Chow 1999;Dale et al 2000;Turner 2000, 2001;Burkard et al 2001;Diamond et al 2001;Mathews and Turner 2002;Proctor et al 2002;Znosko et al 2002Znosko et al , 2004Chen et al 2004Chen et al , 2005Mathews et al 2004;Vecenie and Serra 2004;Bourdélat-Parks and Wartell 2005;…”

Effects of magnesium ions on the stabilization of RNA oligomers of defined structures

“…The buffer for the melting studies was 0+1 M NaCl, 10 mM cacodylic acid, pH 7, with varying concentrations of magnesium ion+ Single-stranded extinction coefficients were calculated from the extinction coefficients for dinucleotide monophosphate and nucleosides (Borer, 1975;Richards, 1975)+ Strand concentrations were determined from high-temperature absorbance at 280 nm+ Absorbance versus temperature curves were measured at 280 nm with a heating or cooling rate of 1+0 8C min Ϫ1 , on a Uvikon or a Beckman DU 640 spectrophotometer as described previously (Serra et al+, 1994)+ Each data point represents the average of 10-20 melts of the oligomer+ The oligomer concentrations were varied over at least a 50-fold range between 1 mM and 10 mM+ Thermodynamics parameters for the oligomers were determined from both the average of the individual melt curves and plots of the reciprocal melting temperature (T M Ϫ1 ) versus the logarithm of the strand concentration (log C t /4) for non-self-complementary se-quences+ Tables with the thermodynamics for each oligomer at the various magnesium ion concentrations investigated are available at http://webpub+alleg+edu/employee/m/mserra/ professional/publications+shtml and http://www-ibmc+u-strasbg+ fr/upr9002/westhof/+ Absorbance versus temperature profiles were fit to a twostate model with sloping base lines by using a nonlinear least squares program (McDowell & Turner, 1996)+ Thermodynamic parameters for duplex formation were obtained from the averages of the fits of the individual melting curves and by plotting the reciprocal of the melting temperature T M…”