Understanding the forces driving protein folding and aggregation is an essential step in developing means for controlling these important processes. Amide hydrogen exchange, coupled with mass spectrometry, has become an important method for studying protein unfolding and refolding. To extend procedures developed to study unfolding of relatively soluble proteins to less soluble, aggregation-pron...

Molecular dynamics simulations of protein folding and unfolding are often carried out at temperatures (400-600 K) that are much higher than physiological or room temperature to speed up the (un)folding process. Use of such high temperatures changes both the protein and solvent properties considerably, compared to physiological or room temperature. Water models designed for use in conjunction wi...

The capabilities of contemporary differential scanning and isothermal titration microcalorimetry for studying the thermodynamics of protein unfolding/refolding and their association with partners, particularly target DNA duplexes, are considered. It is shown that the predenaturational changes of proteins must not be ignored in studying the thermodynamics of formation of their native structure a...

While evidence is mounting that cells exploit protein unfolding for mechanochemical signal conversion (mechanotransduction), what mechanisms are in place to deal with the unwanted consequences of exposing hydrophobic residues upon force-induced protein unfolding? Here, we show that mechanical chaperones exist that can transiently bind to hydrophobic residues that are freshly exposed by mechanic...

The mechanical unfolding of a set of 12 proteins with diverse topologies is investigated using an all-atom constraint-based model. Proteins are represented as polypeptides cross-linked by hydrogen bonds, salt bridges, and hydrophobic contacts, each modeled as a harmonic inequality constraint capable of supporting a finite load before breaking. Stereochemically acceptable unfolding pathways are ...

Cotranslational N-glycosylation can accelerate protein folding, slow protein unfolding, and increase protein stability, but the molecular basis for these energetic effects is incompletely understood. N-glycosylation of proteins at naïve sites could be a useful strategy for stabilizing proteins in therapeutic and research applications, but without engineering guidelines, often results in unpredi...

According to the "old view," proteins fold along well-defined sequential pathways, whereas the "new view" sees protein folding as a highly parallel stochastic process on funnel-shaped energy landscapes. We have analyzed parallel and sequential processes on a large number of molecular dynamics unfolding trajectories of the protein CI2 at high temperatures. Using rigorous statistical measures, we...

This review focuses on the current view of the interaction between the β-barrel scaffold of fluorescent proteins and their unique chromophore located in the internal helix. The chromophore originates from the polypeptide chain and its properties are influenced by the surrounding protein matrix of the β-barrel. On the other hand, it appears that a chromophore tightens the β-barrel scaffold and p...

Protein unfolding occurs when the balance of forces between the protein's interaction with itself and the protein's interaction with its environment is disrupted. The disruption of this balance of forces may be as simple as a perturbance of the normal water structure around the protein. A decrease in the normal water-water interaction will result in an increase in the relative interaction of wa...

We describe a model of cytoskeletal mechanics based on the force-induced conformational change of protein cross-links in a stressed polymer network. Slow deformation of simulated networks containing cross-links that undergo repeated, serial domain unfolding leads to an unusual state-with many cross-links accumulating near the critical force for further unfolding. This state is robust to thermal...