Laser-based inactivation of pathogenic microorganisms

In the context of studying the possibility of inactivation of pathogenic microorganisms, the dynamic transmission spectra of femtosecond laser radiation in the mid-IR range by bacteria of the Pseudomonaus aeruginosa culture planted on a silicon substrate were investigated. Irradiation revealed a blue shift in the characteristic absorption bands of bacteria, indicating the breaking of hydrogen bonds responsible for the formation of the secondary and tertiary structure of the proteins.

Conservation in the Iron Responsive Element Family

Iron responsive elements (IREs) are mRNA stem-loop targets for translational control by the two iron regulatory proteins IRP1 and IRP2. They are found in the untranslated regions (UTRs) of genes that code for proteins involved in iron metabolism. There are ten “classic” IRE types that define the conserved secondary and tertiary structure elements necessary for proper IRP binding, and there are 83 published “IRE-like” sequences, most of which depart from the established IRE model. Here are structurally-guided discussions regarding the essential features of an IRE and what is important for IRE family membership.

Artificial Intelligence in Aptamer–Target Binding Prediction

Aptamers are short single-stranded DNA, RNA, or synthetic Xeno nucleic acids (XNA) molecules that can interact with corresponding targets with high affinity. Owing to their unique features, including low cost of production, easy chemical modification, high thermal stability, reproducibility, as well as low levels of immunogenicity and toxicity, aptamers can be used as an alternative to antibodies in diagnostics and therapeutics. Systematic evolution of ligands by exponential enrichment (SELEX), an experimental approach for aptamer screening, allows the selection and identification of in vitro aptamers with high affinity and specificity. However, the SELEX process is time consuming and characterization of the representative aptamer candidates from SELEX is rather laborious. Artificial intelligence (AI) could help to rapidly identify the potential aptamer candidates from a vast number of sequences. This review discusses the advancements of AI pipelines/methods, including structure-based and machine/deep learning-based methods, for predicting the binding ability of aptamers to targets. Structure-based methods are the most used in computer-aided drug design. For this part, we review the secondary and tertiary structure prediction methods for aptamers, molecular docking, as well as molecular dynamic simulation methods for aptamer–target binding. We also performed analysis to compare the accuracy of different secondary and tertiary structure prediction methods for aptamers. On the other hand, advanced machine-/deep-learning models have witnessed successes in predicting the binding abilities between targets and ligands in drug discovery and thus potentially offer a robust and accurate approach to predict the binding between aptamers and targets. The research utilizing machine-/deep-learning techniques for prediction of aptamer–target binding is limited currently. Therefore, perspectives for models, algorithms, and implementation strategies of machine/deep learning-based methods are discussed. This review could facilitate the development and application of high-throughput and less laborious in silico methods in aptamer selection and characterization.

Stability of uniformly labeled (13C and 15N) cytochrome c and its L94G mutant

Cytochrome c (cyt c) is widely used as a model protein to study (i) folding and stability aspects of the protein folding problem and (ii) structure–function relationship from the evolutionary point of view. Databases of cyts c now contain 285 cyt c sequences from different organisms. A sequence alignment of all these proteins with respect to horse cyt c led to several important conclusions. One of them is that Leu94 is always conserved in all 30 mammalian cyts c. It is known that mutation L94G of the wild type (WT) horse cyt c is destabilizing and mutant exists as molten globule under the native condition (buffer pH 6 and 25 °C). We have expressed and purified uniformly labeled (13C and 15N) and unlabeled WT horse cyt c and its L94G mutant. We report that labeling does not affect the thermodynamic stability of proteins. To support this conclusion, the secondary and tertiary structure of each protein in labeled and unlabeled forms was determined by conventional techniques (UV–Vis absorption and circular dichroism spectroscopy).

Features of infrared spectra of blood plasma of patients with dyslipidemia

The paper analyzes the IR spectra of blood plasma from healthy donors, patients with brain infarction and patients with coronary heart disease (CHD). It was found that the structure of the main transport protein of blood plasma – albumin – in the blood plasma of patients with brain infarction, patients with CHD and representatives of the control group is almost identical. It is shown that in the absence of changes in the secondary and tertiary structure of albumin, the increase in binding of anionic hydrophobic metabolites in the blood plasma of patients with dyslipidemia compared to control is due to structural changes in low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL).

Studies on Molecular Interactions between Bovine β-Lactoglobulin and Silver Nanoparticles

Background: Silver Nanoparticles (AgNPs) were found to modulate the fibrillation of Bovine Β-Lactoglobulin (BLG). Objective: To gain an insight regarding the mechanism of BLG aggregation modulation by AgNPs at molecular level, studies on the interactions between BLG and AgNPs were carried out. Methods: Protein-ligand interactions were studied based on Trp fluorescence quenching (at four different temperatures), synchronous and three-dimensional fluorescence and circular dichroism spectroscopy (far-UV and near-UV). Results: Protein-nanoparticles association constant was in the range of 106 -1010 M-1 and the quenching constant was determined as ~107 M-1. Ground state complexation between the protein and nanoparticles was predicted. Change in polarity surrounding the Trp residue was not detected by synchronous and three-dimensional fluorescence spectroscopy. AgNPs caused a global change in the secondary and tertiary structure of the protein as revealed from far-UV and near-UV CD spectroscopy. Enthalpy driven complexation between the protein and nanoparticles indicates the involvement of hydrogen bonding and/or van der Waals interactions. Conclusion: Modulation of BLG aggregation by AgNPs is due to strong binding of the nanoparticles with BLG, which also causes structural perturbations of the protein.

A deep attention network for predicting amino acid signals in the formation of α-helices

The secondary and tertiary structure of a protein has a primary role in determining its function. Even though many folding prediction algorithms have been developed in the past decades — mainly based on the assumption that folding instructions are encoded within the protein sequence — experimental techniques remain the most reliable to establish protein structures. In this paper, we searched for signals related to the formation of [Formula: see text]-helices. We carried out a statistical analysis on a large dataset of experimentally characterized secondary structure elements to find over- or under-occurrences of specific amino acids defining the boundaries of helical moieties. To validate our hypothesis, we trained various Machine Learning models, each equipped with an attention mechanism, to predict the occurrence of [Formula: see text]-helices. The attention mechanism allows to interpret the model’s decision, weighing the importance the predictor gives to each part of the input. The experimental results show that different models focus on the same subsequences, which can be seen as codes driving the secondary structure formation.

NFAT5, which protects against hypertonicity, is activated by that stress via structuring of its intrinsically disordered domain

Nuclear Factor of Activated T cells 5 (NFAT5) is a transcription factor (TF) that mediates protection from adverse effects of hypertonicity by increasing transcription of genes, including those that lead to cellular accumulation of protective organic osmolytes. NFAT5 has three intrinsically ordered (ID) activation domains (ADs). Using the NFAT5 N-terminal domain (NTD), which contains AD1, as a model, we demonstrate by biophysical methods that the NTD senses osmolytes and hypertonicity, resulting in stabilization of its ID regions. In the presence of sufficient NaCl or osmolytes, trehalose and sorbitol, the NFAT5 NTD undergoes a disorder-to-order shift, adopting higher average secondary and tertiary structure. Thus, NFAT5 is activated by the stress that it protects against. In its salt and/or osmolyte-induced more ordered conformation, the NTD interacts with several proteins, including HMGI-C, which is known to protect against apoptosis. These findings raise the possibility that the increased intracellular ionic strength and elevated osmolytes caused by hypertonicity activate and stabilize NFAT5.

Effect of Antioxidants on Heavy Metals Induced Conformational Altera-tion of Cytochrome C And Myoglobin

Background: The exposure to heavy metals due to unrestrained industrialization, pollution and non-degradability imposes a significant risk to human health. Proteins are prime targets of heavy metal stress, however, the underlying mechanisms and its impact on heme proteins is still not entirely clear. Objective: To analyze the deleterious effect of heavy metals such as cadmium, chromium and mercury on conformation of two proteins namely, cytochrome c and myoglobin. The protective effect of glycine and ascorbic acid (animal origin), gallic acid and sesamol (plant origin) on heavy metal exposure was studied. Methods: Far- and near-UV circular dichroism (CD) measurements monitored the changes in secondary and tertiary structure. Absorption Soret spectroscopy study revealed changes in heme-protein interaction. Peroxidase activity has been assayed to measure the absorption of tetraguaiacol. The interaction of heme proteins with different heavy metals was done using docking study. Result: Far- and near–UV CD measurements reveal that heavy metals disrupt the secondary and tertiary structure of heme proteins. Antioxidants counteract the deleterious effect of heavy metals. Absorption spectroscopy revealed changes in the Soret region of these heme proteins. Changes in peroxidase activity was observed on addition of heavy metals and antioxidants. Molecular docking validated interaction of the heavy metals with proteins with a significant binding affinity (-2.3 kcal/mol). Conclusion: Heavy metals interfered and disrupted both the heme proteins and mercury showed the maximum deleterious effect, further, chromium showed detrimental effect at very small concentration. The antioxidants from animal origin exhibited better protective response than those from plant source.