Approaching Optimal pH Enzyme Prediction with Large Language Models.

Enzymes are widely used in biotechnology due to their ability to catalyze chemical reactions: food making, laundry, pharmaceutics, textile, brewing─all these areas benefit from utilizing various enzymes. Proton concentration (pH) is one of the key factors that define the enzyme functioning and efficiency. Usually there is only a narrow range of pH values where the enzyme is active.

Unraveling viral drug targets: a deep learning-based approach for the identification of potential binding sites.

The coronavirus disease 2019 (COVID-19) pandemic has spurred a wide range of approaches to control and combat the disease. However, selecting an effective antiviral drug target remains a time-consuming challenge. Computational methods offer a promising solution by efficiently reducing the number of candidates.

A community effort in SARS-CoV-2 drug discovery.

The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against COVID-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors.

Structure-based deep learning for binding site detection in nucleic acid macromolecules.

Structure-based drug design (SBDD) targeting nucleic acid macromolecules, particularly RNA, is a gaining momentum research direction that already resulted in several FDA-approved compounds. Similar to proteins, one of the critical components in SBDD for RNA is the correct identification of the binding sites for putative drug candidates. RNAs share a common structural organization that, together with the dynamic nature of these molecules, makes it challenging to recognize binding sites for small molecules.

Protein-Peptide Binding Site Detection Using 3D Convolutional Neural Networks.

Peptides and peptide-based molecules represent a promising therapeutic modality targeting intracellular protein-protein interactions, potentially combining the beneficial properties of biologics and small-molecule drugs. Protein-peptide complexes occupy a unique niche of interaction interfaces with respect to protein-protein and protein-small molecule complexes. Protein-peptide binding site identification resembles image object detection, a field that had been revolutionalized with computer vision techniques.

Spatiotemporal identification of druggable binding sites using deep learning.

Identification of novel protein binding sites expands druggable genome and opens new opportunities for drug discovery. Generally, presence or absence of a binding site depends on the three-dimensional conformation of a protein, making binding site identification resemble the object detection problem in computer vision. Here we introduce a computational approach for the large-scale detection of protein binding sites, that considers protein conformations as 3D-images, binding sites as objects on these images to detect, and conformational ensembles of proteins as 3D-videos to analyze.

Computational design for thermostabilization of GPCRs.

GPCR superfamily is the largest clinically relevant family of targets in human genome; however, low thermostability and high conformational plasticity of these integral membrane proteins make them notoriously hard to handle in biochemical, biophysical, and structural experiments. Here, we describe the recent advances in computational approaches to design stabilizing mutations for GPCR that take advantage of the structural and sequence conservation properties of the receptors, and employ machine learning on accumulated mutation data for the superfamily. The fast and effective computational tools can provide a viable alternative to existing experimental mutation screening and are poised for further improvements with expansion of thermostability datasets for training the machine learning models.

[Protective effect of selank on the model of mnestic function violation induced by pharmacological blockade of protein synthesis].

We have studied the ability of peptide anxiolytic selank (Thr-Lyz-Pro-Arg-Pro-Gly-Pro) to compensate for mnestic dysfunction caused by the administration of actinomycin D, which inhibits protein synthesis by blocking DNA-dependent RNA polymerase. The experiments were performed on white rats with acquired adaptive ability of spatial visual orientation in a 16-door labyrinth. The learning was based on the avoidance of electric skin irritation at alternating sites of escape reaction (site reflex).

[The role of opioid system in peculiarities of anti-anxiety effect of peptide anxiolytic selank].

Peculiarities of the anxiolytic effects of selank (heptapeptide analog of taftsin) under reduced activity of opioid system upon acute administration of naloxone have been studied in BALB/C and C57BL/6 inbred mice with high and low levels of anxiety, with passive and active emotional stress reaction phenotypes in the open field (OF) test. Selank (0.25 mg/kg, i.

[Excretion of extracellular membrane nanovesicles by aeromonas].

Aim: Study of extracellular membrane nanovesicles production by Aeromonas hydrophila and Aeromonas salmonicida bacteria on a subcellular level.

Materials And Methods: 4 strains of A. hydrophila: 342-1, E 8-8, H 336 and H 1-6-05 and 1 strain of A.

[Experimental optimization of learning and memory processes by selank].

The effect of selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), which is a synthetic derivative of the endogenous tetrapeptide tuftsin (stable with respect to tissue peptidases), on the learning and memory processes and metabolism of serotonin (5-HT) have been experimentally studied on Wistar rats. The animals were trained with food reward in 30 trials per day. Selank (300 microg/kg) or saline were injected after the 10th trial.

[Comparison of the effects of selank and tuftsin on the metabolism of serotonin in the brain of rats pretreated with PCPA].

Effects of the peptide drugs selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) and tuftsin (Thr-Lys-Pro-Arg) on the metabolism of serotonin (5-hydroxytryptamine, 5-HT) in the brain of Wistar rats preliminarily treated with the 5-HT-synthesis inhibitor p-chlorophenylalanine (PCPA, 320 mg/kg, i.p., 4 days before experiment) have been studied on a group of 87 matured rats.

Effect of selank on cognitive processes after damage inflicted to the cerebral catecholamine system during early ontogeny.

Effects of selank on learning, memory, and attention to sensory stimuli of different modality were studied in adult Wistar rats treated with 6-hydroxydopamine (neurotoxin selectively damaging catecholaminergic neurons and their terminals) during the first 3 days of life. Selank (300 microg/kg) restored cognitive processes disordered by chronic artificial inhibition of the cerebral catecholaminergic system.

[Effects of heptapeptide selank on genetically-based and situation-provoked symptoms of depression in behavior in WAG/Rij and Wistar rats, and in BALB/c mice].

A synthetic derivative of the endogenous peptide tuftsin heptapeptide selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) possesses an anxiolytic and psychostimulant effect, and represents a working element of a new peptide drug having completed the third phase of the clinical testing as a selective anxiolytic. The neurobiochemical spectrum of selank action combines mechanisms which are characteristics of antidepressants and psychostimulants: activation of the brain monoaminergic systems, dopamine synthesis and turnover, and modulation of the tyrosine hydroxylase activity. The aim of this study was to investigate the effect of selank in a new model of inherited (genetically-based) symptoms of depression in behavior of inbred WAG/Rij rats in comparison with its effect on situation-provoked symptoms of depression in behavior of BALB/c mice.

[Compensatory effect of selank on the mnestic functions disturbed by neurotoxic damage of the noradrenergic system of the rat brain].

It has been shown that the peptide anxiolytic drug Selank recovers learning and memory impaired by damage of the noradrenergic (NA) brain system in Wistar rats after injection of the NA-synthesis inhibitor disulfiram, administration of neurotoxic compound 6-OHDA, or a combined induction of hypoxic hypoxia and hypercapnia. The main component of the Selank action is the stimulation of the search reflex aimed to distinguish an adequate adaptive response in the first trials of the learning session. The enhancement of memory consolidation and retrieval shows evidence for stimulation of the brain motivation mechanisms impaired by the NA system damage.

Use of Selank to correct measures of integrative brain activity and biogenic amine levels in adult rats resulting from antenatal hypoxia.

The effects of Selank, the active component of which is the heptapeptide Thr-Lys-Pro-Arg-Pro-Gly-Pro, which includes the tetrapeptide tuftsin and three natural levorotatory amino acids, on behavior and brain serotonin and noradrenaline levels were studied in adult rats subjected to antenatal hypoxia on days 14-16 of gestation. Administration of Selank (300 microg/kg, i.p.

[Early and progressing alcohol cardiomyopathy].

The subjects of the study were 10 young men who had taken about 40 g of alcohol (group 1) and 26 ones who had taken more than 80 g (group 2) one day before the hospitalization. Heart changes on days 3, 4, and 5 after the alcohol intake were studied using ECG, radiography, and ultrasonography; some functional tests reflecting hepatic and renal condition were performed as well. No changes were found in group 1, while certain functional ECG changes were revealed in group 2 patients; these changes were associated with acute toxic alcohol myocardial dystrophy.

[Selank-induced normalizing effects on the integrative brain activity and biogenic amine level disorders due to antenatal hypoxia].

The effects of Selank synthetic analog of Tuftsin, representing the heptapeptide forming Thr-Lys-Pro-Arg-Pro-Gly-Pro, on behavior and serotonin/noradrenalin concentrations in brain were investigated in adult rats exposed to hypoxia during 14-16 days of gestation. It was revealed that injection of Selank (300 mkg/kg, i/p) increased 2--3-fold (p < 0.01) the sensory attention, facilitated 1.

Seasonal effects of Selank on the behavior of hibernating animals.

We studied the seasonal effects of peptide preparation Selank on orientation and exploratory activity in 36 arctic ground squirrels Citellus undulatus in the open-field and hole-board tests. Selank most significantly increased behavioral activity of hibernating animals in the spring and fall. The test peptide had no effect on locomotor activity of animals.

[Arterial hypertension: problems of maintenance therapy].

Aim: To study hypotensive reactions in patients taking hypotensive drugs and to specify peculiarities of blood pressure elevation in patients with a long history of taking hypotensive drugs, especially atenolol.

Material And Methods: ECG, ultrasound investigation, chest x-ray, cholesterol, lipoprotein, urea, creatinine assays, tests for serum transaminase and transpeptidase activity were made in 200 patients with essential hypertension of the 1-3 degree (110 males, 90 females, age 30-80 years) to elucidate effects of 24-h and prolonged administration of peripheral vasodilators, diuretics, beta-adrenoblockers. The following drugs were given: nitroglycerin (sublingually, 0.

[Effects of the new peptide anxiolytic drug selank on the cardiovascular system functioning and respiration in cats].

The effects of the new heptapeptide anxiolytic drug selank (300 mg/kg, i.v.) on the arterial pressure (AP), cerebral blood flow, heart rhythm, respiration, and the AP depression induced by acetylcholine injections was recorded in narcotized male cats.

Selank and short peptides of the tuftsin family in the regulation of adaptive behavior in stress.

White laboratory male rats, inbred male C57BL/6 and Balb/c mice, and male Wistar rats, all previously divided on the basis of the type of emotional reactivity, were used to compare the effects of ten peptide compounds of the tuftsin family and Selank on the behavioral manifestations of emotional stress created by a conflict situation. Peptides were shown to have positive emotional effects and antistress actions. Individual physiologically significant effects were seen, due to the molecular structures of the study peptides and/or their degradation fragments.

The optimizing action of the synthetic peptide Selank on a conditioned active avoidance reflex in rats.

The actions of the synthetic heptapeptide preparation Selank on learning and memory processes in rats with initially low levels of learning ability were compared with those in normal rats, using a method based on acquisition of a conditioned active avoidance reflex, with repeated administration of peptide 15 min before the start of training sessions for four days. The effects of Selank (300 microg/kg) were compared with the effects of the nootrope piracetam (400 mg/kg). These experiments showed that Selank significantly activated the learning process in rats with initially poor learning ability, with effects apparent after first dose on training day 1.