Over the past three decades the protein folding field has undergone monumental changes. Originally a purely academic question, how a protein folds has now become vital in understanding diseases and our abilities to rationally manipulate cellular life by engineering protein folding pathways. We review and contrast past and recent developments in the protein folding field. Specifically, we discus...

The folding of a protein-like heteropolymer is studied by using direct simulation of a lattice model that folds rapidly to a well-defined "native" structure. The details of each molecular folding event depend on the random initial conformation as well as the random thermal fluctuations of the polymer. By analyzing the statistical properties of hundreds of folding events, a classical folding "pa...

The folding of a protein-like heteropolymer is studied by direct simulation of a lattice model that folds rapidly to a well-defined “native” structure. The details of each molecular folding event depend on the random initial conformation as well as the random thermal fluctuations of the polymer. By analysing the statistical properties of hundreds of folding events, a classical folding “pathway”...

An off-lattice 46-bead model of a small all-beta protein has been recently criticized for possessing too many traps and long-lived intermediates compared with the folding energy landscape predicted for real proteins and models using the principle of minimal frustration. Using a novel sequence design approach based on threading for finding beneficial mutations for destabilizing traps, we propose...

The equilibrium folding of the catalytic domain of Bacillus subtilis RNase P RNA is investigated by single-molecule fluorescence resonance energy transfer (FRET). Previous ensemble studies of this 255-nucleotide ribozyme described the equilibrium folding with two transitions, U-to-I(eq)-to-N, and focused on the I(eq)-to-N transition. The present study focuses on the U-to-I(eq) transition. Compa...

Folding of the Tetrahymena self-splicing RNA into its active conformation involves a set of discrete intermediate states. The Mg2+-dependent equilibrium transition from the intermediates to the native structure is more cooperative than the formation of the intermediates from the unfolded states. We show that the degree of cooperativity is linked to the free energy of each transition and that th...

Despite the ubiquitous nature of misfolded intermediates in RNA folding, little is known about their physical properties or the folding transitions that allow them to continue folding productively. Folding of the Tetrahymena group I ribozyme includes sequential accumulation of two intermediates, termed I(trap) and misfolded (M). Here, we probe the structure and folding transition of I(trap) and...

Most single-domain proteins show cooperative unfolding transitions at equilibrium: the cooperativity of protein folding makes it difficult to populate non-native protein structures [1,2]. Nevertheless, protein folding intermediates are known to exist [1,2] and alternative protein conformations have been demonstrated by numerous methods [2-41. A long-standing problem is how to populate non-nativ...