The RNA folding trajectory features numerous off-pathway folding traps, which represent conformations that are often equally as stable as the native functional ones. Therefore, the conversion between these off-pathway structures and the native correctly folded ones is the critical step in RNA folding. This process, referred to as RNA refolding, is slow, and is represented by a transition state ...

Mg2+ ions are very effective at stabilizing tertiary structures in RNAs. In most cases, folding of an RNA is so strongly coupled to its interactions with Mg2+ that it is difficult to separate free energies of Mg2+-RNA interactions from the intrinsic free energy of RNA folding. To devise quantitative models accounting for this phenomenon of Mg2+-induced RNA folding, it is necessary to independen...

RNA folding is an essential aspect underlying RNA-mediated cellular processes. Many RNAs, including large, multi-domain ribozymes, are capable of folding to the native, functional state without assistance of a protein cofactor in vitro. In the cell, trans-acting factors, such as proteins, are however known to modulate the structure and thus the fate of an RNA. DEAD-box proteins, including Mss11...

We introduce here a heuristic approach to kinetic RNA folding that constructs secondary structures by stepwise combination of building blocks. These blocks correspond to subsequences and their thermodynamically optimal structures. These are determined by the standard dynamic programming approach to RNA folding. Folding trajectories are modeled at base-pair resolution using the Morgan-Higgs heur...

The inverse folding approach is a powerful tool in protein structure prediction when the native state of a sequence adopts one of the known protein folds. This is because some proteins show strong sequence-structure specificity in inverse folding experiments that allow gaps and insertions in the sequence-structure alignment. In those cases when structures similar to their native folds are inclu...

We report the characterization of the energy landscape and the folding/unfolding thermodynamics of a hyperstable RNA tetraloop obtained through high-performance molecular dynamics simulations at microsecond timescales. Sampling of the configurational landscape is conducted using temperature replica exchange molecular dynamics over three isochores at high, ambient, and negative pressures to dete...

Structured RNA molecules play roles in central biological processes and understanding the basic forces and features that govern RNA folding kinetics and thermodynamics can help elucidate principles that underlie biological function. Here we investigate one such feature, the specific interaction of monovalent cations with a structured RNA, the P4-P6 domain of the Tetrahymena ribozyme. We employ ...

Helical junctions are extremely common motifs in naturally occurring RNAs, but little is known about the thermodynamics that drive their folding. Studies of junction folding face several challenges: non-two-state folding behavior, superposition of secondary and tertiary structural energetics, and drastically opposing enthalpic and entropic contributions to folding. Here we describe a thermodyna...

We describe a dynamic programming algorithm for predicting optimal RNA secondary structure, including pseudoknots. The algorithm has a worst case complexity of O(N6) in time and O(N4) in storage. The description of the algorithm is complex, which led us to adopt a useful graphical representation (Feynman diagrams) borrowed from quantum field theory. We present an implementation of the algorithm...

A linear segment in which a number of pairs of intervals of equal length are identified as potential stems is the subject of a folding problem analogous to inference of RNA secondary structure. A quantity of free energy (or equivalently, energy per unit length) is associated with each stem, and the various types of loops are assigned energy costs as a function of their lengths. Inference of sta...