The results of boxed dynamics (BXD) fully atomistic simulations of protein unfolding by atomic force microscopy (AFM) in both force clamp (FC) and velocity clamp (VC) modes are reported. In AFM experiments the unfolding occurs on a time scale which is too long for standard atomistic molecular dynamics (MD) simulations, which are usually performed with the addition of forces which exceed those o...

Herein we describe the results of molecular dynamics simulations of the bovine pancreatic trypsin inhibitor (BPTI) in solution at a variety of temperatures both with and without disulfide bonds. The reduced form of the protein unfolded at high temperature to an ensemble of conformations with all the properties of the molten globule state. In this account we outline the structural details of the...

We propose a simple approach, based on the minimization of the total (entropic plus unfolding) energy of a two-state system, describing the stretch-induced unfolding of macromolecules (proteins, silks, nanopolymers, DNA/RNA). The model is fully analytical and enlightens the role of the different energetic components regulating the unfolding evolution. As an explicit example of application we co...

A double-tweezer setup is used to induce mechanical stress in systems of molecular biology. A double strand of DNA is first stretched and the data is compared to precedent experiments to check the experimental setup. Then a short foldable fragment of RNA is probed; the typical unfolding/refolding hysteresis behaviour of this kind of construction is shown and followed by a study of its elasticit...

Arginine kinase plays an important role in the cellular energy metabolism of invertebrates. Dimeric arginine kinase (dAK) is unique in some marine invertebrates. The effects of Zn²(+) on the unfolding and aggregation of dAK from the sea cucumber Stichopus japonicus were investigated. Our results indicated that Zn²(+) caused dAK inactivation accompanied by conformational unfolding, the exposure ...

This paper discusses learning of Constraint Logic Programs using unfolding and slicing technique. The transformation rule for unfolding together with clause removal is a method for specialization of Logic Programs. Slicing is a program analysis technique originally developed for imperative languages. It facilitates the understanding of data flow and debugging. This paper formulates the semantic...

Unfolding is an essential process during translocation of preproteins into mitochondria; however, controversy exists as to whether mitochondria play an active role in unfolding. We have established an in vitro system with a kinetic saturation of the mitochondrial import machinery, yielding translocation rates comparable to in vivo import rates. Preproteins with short N-terminal segments in fron...

Cellular compartmentalization requires machinery capable of translocating polypeptides across membranes. In many cases, transported proteins must first be unfolded by means of the proton motive force and/or ATP hydrolysis. Anthrax toxin, which is composed of a channel-forming protein and two substrate proteins, is an attractive model system to study translocation-coupled unfolding, because the ...

Unfolding of proteins by forced stretching with atomic force microscopy or laser tweezer experiments complements more classical techniques using chemical denaturants or temperature. Forced unfolding is of particular interest for proteins that are under mechanical stress in their biological function. For beta-sandwich proteins (a fibronectin type III and an immunoglobulin domain), both of which ...

We discuss the use of a structure based Cα-Go model and Langevin dynamics to study in detail the mechanical properties and unfolding pathway of the titin I27 domain. We show that a simple Go-model does detect correctly the origin of the mechanical stability of this domain. The unfolding free energy landscape parameters x(u) and ΔG(‡), extracted from dependencies of unfolding forces on pulling s...