It has long been thought that degeneracy in unfolding only concerned non-metric unfolding. Recently, Busing, Groenen, and Heiser have established that degeneracy occurs for all transformations that include estimation of an intercept and a slope. Consequently, degeneracy also plagues metric unfolding, since one member of the metric transformation family, the interval transformation, includes est...

dialysis-related amyloidosis (dra) is characterized by accumulation of amyloid β2-microglobulin (β2m) in the interstitial matrix. matrix substances such as heparin have reportedly been strongly implicated in the pathogenesis of dialysis-related amyloidosis. in clinical setting of hemodialysis, two types of heparin, i.e., high and low molecular heparin (h.m.h. and l.m.h.) have been routinely use...

Molecular dynamics simulations of protein folding or unfolding, unlike most in vitro experimental methods, are performed on a single molecule. The effects of neighboring molecules on the unfolding/folding pathway are largely ignored experimentally and simply not modeled computationally. Here, we present two all-atom, explicit solvent molecular dynamics simulations of 32 copies of the Engrailed ...

In this thesis we investigate the relationship between finite terms in λletrec, the λ-calculus with letrec, and the infinite λ-terms they express. We say that a λletrec-term expresses a λ-term if the latter can be obtained as an infinite unfolding of the former. Unfolding is the process of substituting occurrences of function variables by the right-hand side of their definition. We consider the...

In the AAA+ ClpXP protease, ClpX uses the energy of ATP binding and hydrolysis to unfold proteins before translocating them into ClpP for degradation. For proteins with C-terminal ssrA tags, ClpXP pulls on the tag to initiate unfolding and subsequent degradation. Here, we demonstrate that an initial step in ClpXP unfolding of the 11-stranded β barrel of superfolder GFP-ssrA involves extraction ...

Screening for pharmaceutically viable stability from measurements of thermally induced protein unfolding and short-term accelerated stress underpins much molecule design, selection, and formulation in the pharmaceutical biotechnology industry. However, the interrelationships among intrinsic protein conformational stability, thermal denaturation, and pharmaceutical stability are complex. There a...

The folding and stability of transmembrane proteins is a fundamental and unsolved biological problem. Here, single bacteriorhodopsin molecules were mechanically unfolded from native purple membranes using atomic force microscopy and force spectroscopy. The energy landscape of individual transmembrane alpha helices and polypeptide loops was mapped by monitoring the pulling speed dependence of th...

Membrane proteins are assembled through balanced interactions among proteins, lipids and water. Studying their folding while maintaining the native lipid environment is necessary but challenging. Here we present methods for analyzing key elements of membrane protein folding including thermodynamic stability, compactness of the unfolded state and folding cooperativity under native conditions. Th...

We use single silicon nitride nanopores to study folded, partially folded, and unfolded single proteins by measuring their excluded volumes. The DNA-calibrated translocation signals of beta-lactoglobulin and histidine-containing phosphocarrier protein match quantitatively with that predicted by a simple sum of the partial volumes of the amino acids in the polypeptide segment inside the pore whe...

The pressure behavior of proteins may be summarized as a the pressure-induced disordering of their structures. This thermodynamic parameter has effects on proteins that are similar but not identical to those induced by temperature, the other thermodynamic parameter. Of particular importance are the intermolecular interactions that follow partial protein unfolding and that give rise to the forma...