Structure-Based Discovery of High-Affinity Small Molecule Ligands and Development of Tool Probes to Study the Role of Chitinase-3-Like Protein 1.

Chitinase-3-like-1 (CHI3L1), also known as YKL-40, is a glycoprotein linked to inflammation, fibrosis, and cancer. This study explored CHI3L1's interactions with various oligosaccharides using microscale thermophoresis (MST) and AlphaScreen (AS). These investigations guided the development of high-throughput screening assays to assess interference of small molecules in binding between CHI3L1 and biotinylated small molecules or heparan sulfate-based probes.

Novel orally bioavailable piperidine derivatives as extracellular arginase inhibitors developed by a ring expansion.

Arginase is a multifaced enzyme that plays an important role in health and disease being regarded as a therapeutic target for the treatment of various pathological states such as malignancies, asthma, and cardiovascular disease. The discovery of boronic acid-based arginase inhibitors in 1997 revolutionized attempts of medicinal chemistry focused on development of drugs targeting arginase. Unfortunately, these very polar compounds had limitations such as analysis and purification without chromophores, synthetically challenging space, and poor oral bioavailability.

Vehicle Detection and Recognition Approach in Multi-Scale Traffic Monitoring System via Graph-Based Data Optimization.

Over the past few years, significant investments in smart traffic monitoring systems have been made. The most important step in machine learning is detecting and recognizing objects relative to vehicles. Due to variations in vision and different lighting conditions, the recognition and tracking of vehicles under varying extreme conditions has become one of the most challenging tasks.

Advanced Feature Extraction Methods from Images of Drillings in Melamine Faced Chipboard for Automatic Diagnosis of Drill Wear.

In this paper, a novel approach to evaluation of feature extraction methodologies is presented. In the case of machine learning algorithms, extracting and using the most efficient features is one of the key problems that can significantly influence overall performance. It is especially the case with parameter-heavy problems, such as tool condition monitoring.

Tracking Topological and Electronic Effects on the Folding and Stability of Guanine-Deficient RNA G-Quadruplexes, Engineered with a New Computational Tool for De Novo Quadruplex Folding.

The initial aim of this work was to elucidate the mutual influence of different single-stranded segments (loops and caps) on the thermodynamic stability of RNA G-quadruplexes. To this end, we used a new NAB-GQ-builder software program, to construct dozens of two-tetrad G-quadruplex topologies, based on a designed library of sequences. Then, to probe the sequence-morphology-stability relationships of the designed topologies, we performed molecular dynamics simulations.

New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer's Disease Research.

Viral pneumonia caused by highly infectious SARS-CoV-2 poses a higher risk to older people and those who have underlying health conditions, including Alzheimer's disease. In this work we present newly designed tacrine-based radioconjugates with physicochemical and biological properties that are crucial for the potential application as diagnostic radiopharmaceuticals. A set of ten tacrine derivatives was synthesized, labelled with gallium-68 and fully characterized in the context of their physicochemical properties.

Novel Cyclopentaquinoline and Acridine Analogs as Multifunctional, Potent Drug Candidates in Alzheimer's Disease.

A series of new cyclopentaquinoline derivatives with 9-acridinecarboxylic acid and a different alkyl chain length were synthesized, and their ability to inhibit cholinesterases was evaluated. All designed compounds, except derivative , exhibited a selectivity for butyrylcholinesterase (BuChE) with IC values ranging from 103 to 539 nM. The derivative revealed the highest inhibitory activity towards BuChE (IC = 103.

Multiclass Image Classification Using GANs and CNN Based on Holes Drilled in Laminated Chipboard.

The multiclass prediction approach to the problem of recognizing the state of the drill by classifying images of drilled holes into three classes is presented. Expert judgement was made on the basis of the quality of the hole, by dividing the collected photographs into the classes: "very fine," "acceptable," and "unacceptable." The aim of the research was to create a model capable of identifying different levels of quality of the holes, where the reduced quality would serve as a warning that the drill is about to wear down.

The universality of enzymatic rate-temperature dependency.

Organismal adaptation to extreme temperatures yields enzymes with distinct configurational stabilities, including thermophilic and psychrophilic enzymes, which are adapted to high and low temperatures, respectively. These enzymes are widely assumed to also have unique rate-temperature dependencies. Thermophilic enzymes, for example, are considered optimal at high temperatures and effectively inactive at low temperatures due to excess rigidity.

Discovery of novel potent ΔF508-CFTR correctors that target the nucleotide binding domain.

The deletion of Phe508 (ΔF508) in the first nucleotide binding domain (NBD1) of CFTR is the most common mutation associated with cystic fibrosis. The ΔF508-CFTR mutant is recognized as improperly folded and targeted for proteasomal degradation. Based on molecular dynamics simulation results, we hypothesized that interaction between ΔF508-NBD1 and housekeeping proteins prevents ΔF508-CFTR delivery to the plasma membrane.

Direct targeting of Arabidopsis cysteine synthase complexes with synthetic polypeptides to selectively deregulate cysteine synthesis.

Biosynthesis of cysteine is one of the fundamental processes in plants providing the reduced sulfur for cell metabolism. It is accomplished by the sequential action of two enzymes, serine acetyltransferase (SAT) and O-acetylserine (thiol) lyase (OAS-TL). Together they constitute the hetero-oligomeric cysteine synthase (CS) complex through specific protein-protein interactions influencing the rate of cysteine production.

Catalytic metal ion rearrangements underline promiscuity and evolvability of a metalloenzyme.

Although largely deemed as structurally conserved, catalytic metal ion sites can rearrange, thereby contributing to enzyme evolvability. Here, we show that in paraoxonase-1, a lipo-lactonase, catalytic promiscuity and divergence into an organophosphate hydrolase are correlated with an alternative mode of the catalytic Ca(2+). We describe the crystal structures of active-site mutants bearing mutations at position 115.

Influence of macromolecular crowding on protein-protein association rates--a Brownian dynamics study.

The high total concentration of macromolecules, often referred to as macromolecular crowding, is one of the characteristic features of living cells. Macromolecular crowding influences interactions between many types of macromolecules, with consequent effects on, among others, the rates of reactions occurring in the cell. Simulations to study the influence of crowding on macromolecular association rate were performed using a modified Brownian dynamics protocol.

MOFOID--not only the protein modeling server.

MOFOID is a new server developed mainly for automated modeling of protein structures by their homology to the structures deposited in the PDB database. Selection of a template and calculation of the alignment is performed with the Smith-Waterman or Needleman-Wunsch algorithms implemented in the EMBOSS package. The final model is built and optimised with programs from the JACKAL package.