Exploring Compactness and Dynamics of Apomyoglobin.

Hydrogen-deuterium exchange mass spectrometry (HDX-MS) approach has become a valuable analytical complement to traditional methods. HDX-MS allows the identification of dynamic surfaces in proteins. We have shown that the introduction of various mutations into the amino acid sequence of whale apomyoglobin (apoMb) leads to a change in the number of exchangeable hydrogen atoms, which is associated with a change in its compactness in the native-like condition.

Comparison of deep learning models with simple method to assess the problem of antimicrobial peptides prediction.

Antibiotic-resistant strains are an emerging threat to public health. The usage of antimicrobial peptides (AMPs) is one of the promising approaches to solve this problem. For the development of new AMPs, it is necessary to have reliable prediction methods.

The Strategies of Development of New Non-Toxic Inhibitors of Amyloid Formation.

In recent years, due to the aging of the population and the development of diagnostic medicine, the number of identified diseases associated with the accumulation of amyloid proteins has increased. Some of these proteins are known to cause a number of degenerative diseases in humans, such as amyloid-beta (Aβ) in Alzheimer's disease (AD), α-synuclein in Parkinson's disease (PD), and insulin and its analogues in insulin-derived amyloidosis. In this regard, it is important to develop strategies for the search and development of effective inhibitors of amyloid formation.

Knomics-Biota - a system for exploratory analysis of human gut microbiota data.

Background: Metagenomic surveys of human microbiota are becoming increasingly widespread in academic research as well as in food and pharmaceutical industries and clinical context. Intuitive tools for investigating experimental data are of high interest to researchers.

Results: Knomics-Biota is a web-based resource for exploratory analysis of human gut metagenomes.

[Anomalous Kinetics of Amyloidogenesis Suggest a Competition between Oligomers and Fibrils].

Meisl et al. have recently observed an anomalous dependence of the amyloid formation rate on the protein concentration. A novel mechanism of fibril growth has been proposed by Meisl et al.

The Mechanism Underlying Amyloid Polymorphism is Opened for Alzheimer's Disease Amyloid-β Peptide.

It has been demonstrated using Aβ40 and Aβ42 recombinant and synthetic peptides that their fibrils are formed of complete oligomer ring structures. Such ring structures have a diameter of about 8-9 nm, an oligomer height of about 2- 4 nm, and an internal diameter of the ring of about 3-4 nm. Oligomers associate in a fibril in such a way that they interact with each other, overlapping slightly.

Structural model of amyloid fibrils for amyloidogenic peptide from Bgl2p-glucantransferase of S. cerevisiae cell wall and its modifying analog. New morphology of amyloid fibrils.

We performed a comparative study of the process of amyloid formation by short homologous peptides with a substitution of aspartate for glutamate in position 2 - VDSWNVLVAG (AspNB) and VESWNVLVAG (GluNB) - with unblocked termini. Peptide AspNB (residues 166-175) corresponded to the predicted amyloidogenic region of the protein glucantransferase Bgl2 from the Saccharomyces cerevisiae cell wall. The process of amyloid formation was monitored by fluorescence spectroscopy (FS), electron microscopy (EM), tandem mass spectrometry (TMS), and X-ray diffraction (XD) methods.

Determination of Size of Folding Nuclei of Fibrils Formed from Recombinant Aβ(1-40) Peptide.

We have developed a highly efficient method for purification of the recombinant product Aβ(1-40) peptide. The concentration dependence of amyloid formation by recombinant Aβ(1-40) peptide was studied using fluorescence spectroscopy and electron microscopy. We found that the process of amyloid formation is preceded by lag time, which indicates that the process is nucleation-dependent.

Smooth muscle titin forms in vitro amyloid aggregates.

Amyloids are insoluble fibrous protein aggregates, and their accumulation is associated with amyloidosis and many neurodegenerative diseases, including Alzheimer's disease. In the present study, we report that smooth muscle titin (SMT; 500 kDa) from chicken gizzard forms amyloid aggregates in vitro This conclusion is supported by EM data, fluorescence analysis using thioflavin T (ThT), Congo red (CR) spectroscopy and X-ray diffraction. Our dynamic light scattering (DLS) data show that titin forms in vitro amyloid aggregates with a hydrodynamic radius (Rh) of approximately 700-4500 nm.

Computational Approaches to Identification of Aggregation Sites and the Mechanism of Amyloid Growth.

This chapter describes computational approaches to study amyloid formation. The first part addresses identification of potential amyloidogenic regions in the amino acid sequences of proteins and peptides. Next, we discuss nucleation and aggregation sites in protein folding and misfolding.

Mechanisms of amyloid fibril formation.

Amyloid and amyloid-like aggregates are elongated unbranched fibrils consisting of β-structures of separate monomers positioned perpendicular to the fibril axis and stacked strictly above each other. In their physicochemical properties, amyloid fibrils are reminiscent of synthetic polymers rather than usual proteins because they are stable to the action of denaturing agents and proteases. Their mechanical stability can be compared to a spider's web, that in spite of its ability to stretch, is stronger than steel.

What handedness and angles between helices has the studied three-helical protein domain?

We have created a new server FoldHandedness. Using this server it is possible: (i) to define the regions of helices from two issues (from the PDB file and using the last version of the DSSP program), (ii) to determine the handedness for any chosen three helices and (iii) to calculate the angle and sign between the chosen pairs of the helices for large proteins and complexes of proteins with DNA or RNA.

How to determine the size of folding nuclei of protofibrils from the concentration dependence of the rate and lag-time of aggregation. II. Experimental application for insulin and LysPro insulin: aggregation morphology, kinetics, and sizes of nuclei.

Insulin is a commonly used protein for studies of amyloidogenesis. There are a few insulin analogues with different pharmacokinetic characteristics, in particular the onset and duration of action. One of them is LysPro insulin.

How to determine the size of folding nuclei of protofibrils from the concentration dependence of the rate and lag-time of aggregation. I. Modeling the amyloid protofibril formation.

The question about the size of nuclei of formation of protofibrils (which constitute mature amyloid fibrils) formed by different proteins and peptides is yet open and debatable because of the absence of solid knowledge of underlying mechanisms of amyloid formation. In this work, a kinetic model of the process of formation of amyloid protofibrils is suggested, which allows calculation of the size of the nuclei using only kinetic data. In addition to the stage of primary nucleation, which is believed to be present in many protein aggregation processes, the given model includes both linear growth of protofibrils (proceeding only at the cost of attaching of monomers to the ends) and exponential growth of protofibrils at the cost of growth from the surface, branching, and fragmentation with the secondary nuclei.

A novel web server predicts amino acid residue protection against hydrogen-deuterium exchange.

Motivation: To clarify the relationship between structural elements and polypeptide chain mobility, a set of statistical analyses of structures is necessary. Because at present proteins with determined spatial structures are much less numerous than those with amino acid sequence known, it is important to be able to predict the extent of proton protection from hydrogen-deuterium (HD) exchange basing solely on the protein primary structure.

Results: Here we present a novel web server aimed to predict the degree of amino acid residue protection against HD exchange solely from the primary structure of the protein chain under study.

Comparison of experimental and theoretical data on hydrogen-deuterium exchange for ten globular proteins.

The number of protons available for hydrogen-deuterium exchange was predicted for ten globular proteins using a method described elsewhere by the authors. The average number of protons replaced by deuterium was also determined by mass spectrometry of the intact proteins in their native conformations. Based on these data, we find that two models proposed earlier agree with each other in estimation of the number of protons replaced by deuterium.

Modeling amyloid fibril formation.

No detailed step-by-step model of protein rearrangements during amyloid structure formation has been presented in the literature. The aim of this work was to design a kinetic model for description of the amyloid formation process on the basis of the most recent experimental data. A general kinetic model is proposed for description of the amyloid formation process including the nucleation mechanism of polymerization with consecutive monomer attachment to oligomer and autocatalytic growth of amyloid aggregates implying all types of exponential growth such as branching, fragmentation, and growth from the surface.