Assessing the reliability of RNA folding using statistical mechanics

RNA folding at elementary step resolution

“…Structures and base pairing density plots for the mfe structure and the metastable conformation of the Qb variant SV11+ The secondary structures and their free energies are shown in the upper part+ In the lower half we show the matrix of base pair probabilities as obtained from the thermodynamic partition function (McCaskill, 1990;Hofacker et al+, 1994) (left) and from kinetic trajectories (right)+ the robustness of most currently available algorithms in predictions on RNA structures (Tacker et al+, 1996) and found that certain statistical properties of the sequenceto-structure map are reproduced quite well, although predictions for individual sequences may be poor (see also Huynen et al+, 1997)+ Similarly, in the context of the present study we expect that generic features are reproduced correctly by our kinetic simulations+ Such features pertain to the relationship between major kinetic properties and the barrier structure of conformational spaces+ Examples considered here emphasized the partition of conformation space into basins of attraction for several dominant structures, and, consequently multiple folding mechanisms and folding time scales+ We also found the existence of dominant metastable states with large basins in the presence of mfe structures that are kinetically far less accessible despite their thermodynamic dominance+…”

Origins and evolution of modern biochemistry: insights from genomes and molecular structure

“…However, the sequence-to-structure mapping of proteins is much more complex and its landscape "holey," with protein conformations missing in vast segments of sequence space. While the neutrality of protein sequence space is much higher than that of RNA [>90% of single amino acid substitutions are neutral (52)], protein structures appear to concentrate in dense clusters (53,54) while RNA structures spread through sparsely connected networks (55).…”

“…A set of character attributes that describe the geometry ("shape" characters that measure for example the length of stems, loops or unpaired segments) and the branching, stability, and uniqueness (plasticity) ["statistical" characters that measure statistical mechanic properties of branching, stability and uniqueness (55,82,134,135)] of the molecules are first identified. These are then encoded in alphanumeric format and used to construct data matrices for phylogenetic analysis.…”

Unique folding of precursor microRNAs: Quantitative evidence and implications for de novo identification

“…Normalized Shannon entropy Q(s) in Equation (1), characterizes the base-pairing probability distribution (BPPD) per base in a sequence s as a chaotic dynamical system (Huynen et al 1997;Schultes et al 1999;Freyhult et al 2005). The local dominance of a single structure within the Boltzmann distribution of alternative secondary structures is strongly correlated with the reliability of the MFE structure.…”