Escherichia coli is one of the most widely used hosts for the production of recombinant proteins. However, very often the target protein accumulates into insoluble aggregates in a misfolded and biologically inactive form. Bacterial inclusion bodies are major bottlenecks in protein production and are hampering the development of top priority research areas such structural genomics. Inclusion bod...

The recent boom in general-purpose computing on graphics processing units (GPGPU) facilitates simulations with high demands on computer resources. Such simulations are typical for macromolecules and nanoparticles of biological importance. Several proteins, instead of folding into biologically active 3D structures, aggregate together forming large fibril structures called amyloid aggregates. Amy...

Mass spectrometry has become a powerful method to study the structure and dynamics of proteins. Hydrogen/deuterium exchange in conjunction with mass spectrometry is now becoming more widely used to monitor conformational changes in proteins, and when combined with proteolytic digestion or gas-phase dissociation, it can provide spatial resolution of structural regions which participate in confor...

Factors controlling the onset and progression of extracellular amyloid diseases remain largely unknown. Central to disease etiology is the efficiency of the endoplasmic reticulum (ER) machinery that targets destabilized mutant proteins for degradation and the enhanced tendency of these variants to aggregate if secreted. We demonstrate that mammalian cells secrete numerous transthyretin (TTR) di...

Current limitations in de novo protein structure prediction and design suggest an incomplete understanding of the interactions that govern protein folding. Here we demonstrate that previously unappreciated hydrogen bonds occur within proteins between the amide proton and carbonyl oxygen of the same residue. Quantum calculations, infrared spectroscopy, and nuclear magnetic resonance spectroscopy...

Sequences rich in glutamine (Q) and asparagine (N) residues often fail to fold at the monomer level. This, coupled to their unusual hydrogen-bonding abilities, provides the driving force to switch between disordered monomers and amyloids. Such transitions govern processes as diverse as human protein-folding diseases, bacterial biofilm assembly, and the inheritance of yeast prions (protein-based...

buckle folds are common traps for hydrocarbon in several contractional provinces. buckle folds form where stratified sequences rest a top salt or some other utterly weak rock as a decollemet zone in units with high competency contrasts by a compressive stress which acted along the length of the rock layers. an important parameter affecting buckle folding of a competent zone above a mobile decol...

This study presents a numerical investigation of the dimerization polyglutamine homo-peptides varying length. It employs PRIME20 intermediate resolution protein model and studies it with flat-histogram type Monte Carlo simulation that gives access to thermodynamic equilibrium this over complete control parameter range (for simulations is temperature). For densities comparable typical in vitro e...

We recently described site-specific pyrene labeling of RNA to monitor Mg(2+)-dependent equilibrium formation of tertiary structure. Here we extend these studies to follow the folding kinetics of the 160-nucleotide P4-P6 domain of the Tetrahymena group I intron RNA, using stopped-flow fluorescence with approximately 1 ms time resolution. Pyrene-labeled P4-P6 was prepared using a new phosphoramid...

Viva the worm ike yin and yang, good things usually come at a cost. If you live longer, then you give up reproductive fitness in return. The merits of this model—termed antagonistic pleiotropy—have been argued by evolutionary biologists for half a century. Some believe that the effort of reproduction is necessarily linked to deterioration characteristic of aging. have challenged the idea by unc...