Psychrophilic, mesophilic, and thermophilic alpha-amylases have been studied as regards their conformational stability, heat inactivation, irreversible unfolding, activation parameters of the reaction, properties of the enzyme in complex with a transition state analog, and structural permeability. These data allowed us to propose an energy landscape for a family of extremophilic enzymes based o...

Dynamic force spectroscopy and steered molecular simulations have become powerful tools for analyzing the mechanical properties of proteins, and the strength of protein-protein complexes and aggregates. Probability density functions of the unfolding forces and unfolding times for proteins, and rupture forces and bond lifetimes for protein-protein complexes allow quantification of the forced unf...

Thermal unfolding of proteins is compared to folding and mechanical stretching in a simple topology-based dynamical model. We define the unfolding time and demonstrate its low-temperature divergence. Below a characteristic temperature, contacts break at separate time scales and unfolding proceeds approximately in a way reverse to folding. Features in these scenarios agree with experiments and a...

This note shows that the hope expressed in [ADL07]—that the new algorithm for edge-unfolding any polyhedral band without overlap might lead to an algorithm for unfolding any prismatoid without overlap—cannot be realized. A prismatoid is constructed whose sides constitute a nested polyhedral band, with the property that every placement of the prismatoid top face overlaps with the band unfolding.

Dynamic force spectroscopy has become indispensable for the exploration of the mechanical properties of proteins. In force-ramp experiments, performed by utilizing a time-dependent pulling force, the peak forces for unfolding transitions in a multimeric protein (D)(N) are used to map the free energy landscape for unfolding for a protein domain D. We show that theoretical modeling of unfolding t...

The usefulness of targeted molecular dynamics (TMD) for the simulation of large conformational transitions is assessed in this work on the unfolding process of chymotrypsin inhibitor 2 (CI2). In TMD the force field is supplemented with a harmonic restraint which promotes either the increase of the conformational distance from the native state or the decrease of the distance from a target unfold...

Clp ATPases are ring-shaped AAA+ motors in the degradation pathway that perform critical actions of unfolding and translocating substrate proteins (SPs) through narrow pores to deliver them to peptidase components. These actions are effected by conserved diaphragm-forming loops found in the central channel of the Clp ATPase hexamer. Conformational changes, that take place in the course of repet...

Protecting osmolytes are widespread small organic molecules able to stabilize the folded state of most proteins against various denaturing stresses in vivo. The osmophobic model explains thermodynamically their action through a preferential exclusion of the osmolyte molecules from the protein surface, thus favoring the formation of intrapeptide hydrogen bonds. Few works addressed the influence ...

Prolyl hydroxylase domain-containing protein 2 (PHD2), as one of the most important regulators of angiogenesis and metastasis of cancer cells, is a promising target for cancer therapy drug design. Progressive studies imply that abnormality in PHD2 function may be due to misfolding. Therefore, study of the PHD2 unfolding pathway paves the way for a better understanding of the influence of PHD2 m...

A simple model is presented for analyzing a set of spectra obtained from spectrophotometric study of protein titration. With this model one can determine the states of (probable) intermediates in the course of protein unfolding. The model is developed based on abundance of native state, intermediate(s) and denatured state, and their contributions to differential absorbance at selected wavelengt...