Biophysics最新文献

The experimentally obtained structures of 48 ACE 2 receptor complexes with RBD of the S protein of the SARS-CoV and SARS-CoV-2 coronaviruses (including mutant forms of the latter) were evaluated, for which the dissociation constants were calculated. To predict the binding affinity, the ProBAN neural network algorithm developed by the authors earlier was used, as well as a number of other Gibbs free energy estimation algorithms: Prodigy, FoldX, DFIRE, and RosettaDock. A comparison of the evaluation results showed that ProBAN demonstrated the best prediction quality (Pearson correlation coefficient was 0.56 and the mean absolute error was 0.7 kcal/mol). The results we obtained suggested a better quality of affinity prediction for other protein–protein complexes as well. Information about the studied complexes and the prediction results are available in the repository at the link: https://github.com/EABogdanova/ProBAN_RBD-ACE2.

The antitumor activity of the N-glycoside derivative indolo[2,3-a]carbazole LCS-1269 with a polysaccharide from Helianthus tuberosus L. as an adjuvant agent was studied on a model of Lewis epidermoid lung carcinoma in mice of F1 hybrids (C₅₇Bl/₆ × DBA/₂). The antitumor effect was assessed by inhibition of tumor growth in treated animals in comparison with controls. As a result, it was found that the therapeutic effect of the combination was higher and longer than in monotherapy, with a decrease in tumor growth of Lewis lung carcinoma by 53–64% up to 28 days of follow-up. The use of the polysaccharide led to an increase in the number of blood cells, leukocytes, lymphocytes, and phagocytes responsible for antitumor immunity. The chemotherapeutic effect of the combination of LCS-1269 and polysaccharide showed a pronounced stable antitumor response against Lewis lung carcinoma in the peripheral blood system of mice with a temporary increase in the number of neutrophils and monocytes on the 12th day of tumor development. The tested compounds obviously stimulated the proliferation of certain phenotypes of neutrophils and monocytes with antitumor activity at an earlier stage of Lewis lung carcinoma development.

The effect of acoustic shock waves on the permeability of membranes of Gram-negative bacteria of P. aeruginosa for the anionic photosensitizer erythrosine has been studied. Shock waves were generated by rapid local heating of the medium, which occurred during the nonradiative relaxation of high electronically excited states of photosensitizer molecules populated by a high-power density laser pulse. It has been shown that the permeability of bacterial membranes increased under the effect of shock waves and erythrosine penetrated into the cells; this was accompanied by an increase in the efficiency of photodynamic action on microorganisms.

A comparative assessment of the binding force of lipopolysaccharide from Yersinia pseudotuberculosis culture with monoclonal antibodies has been carried out using optical tweezers and atomic force microscopy. The features of the two techniques are discussed, which detected significant differences in the measured bond rupture force between a lipopolysaccharide-sensitized probe (a polystyrene microsphere in the case of optical tweezers and a silicon nitride cantilever tip in the case of atomic force microscopy) and a substrate (glass and mica, respectively) coated with monoclonal antibodies. In the case of atomic force microscopy, the tip of the cantilever slides along the surface of the substrate until the piezo stage stops, causing a change in the spatial structure of the sensitins and, as a result, a redistribution of the multiple bonds between the lipopolysaccharide agglomerate and antibodies. When the optical tweezers technique is used there is no significant displacement of the microsphere along the substrate surface and, unlike atomic force microscopy, the rupture of the complex bond between lipopolysaccharide and complementary antibodies is recorded as a single and short-term (1–2 ms) jump in the photodetector signal. The fixed values of the bond rupture force measured by both techniques are relative and vary depending on the selected experimental conditions. It is shown that the nonspecific component of the bond rupture force measured by atomic force microscopy is significantly higher than that determined by optical tweezers.

Fluorescent confocal microscopy has shown the presence of the family of septin proteins types 2, 3, 5, 7, and 9 in the somatic muscle of the earthworm Lumbricus terrestris. Septins of types 2 and 9 lack their specific concentration in the cholinergic synapse zone, whereas septins of types 3 and 5, and especially type 7, have a quantitatively expressed binding localization at the zone of the motor end plate. It is assumed that septins of types 3 and 5 and, above all, type 7 may be participants in the mechanisms of modulation of the quantal secretion of the mediator.

For the first time, the effect of a significant change in the resistance of the aquatic medium of a population of protozoan microorganisms under the influence of electromagnetic radiation from cell phones has been experimentally investigated. The results of the experiment demonstrated the biological nature of the changes occurring in the water–protozoan population system, which indicated the effect of radiation directly on the cells. This conclusion was confirmed by the same time for information exchange between individual participants of the population in the calculation and in the experiment. An extremely low concentration of protozoan cells in the experiment was established, equal to 1000 cells/L, at which the specified effect was observed. It was concluded that the method for detecting changes in the physical properties of the aquatic medium of a population of protozoa under the action of electromagnetic fields can be used to identify the mechanisms of interaction of biological systems with electromagnetic radiation.

In order to further clarify the mechanisms of pharmacological effects of salicylic and acetylsalicylic acids, the interactions of these acids with mitochondrial and erythrocyte membranes were studied and the role of calcium ions/protons in the effects of salicylates was evaluated. Salicylic acid and, to a lesser extent, acetylsalicylic acid at concentrations of 0.5–2.0 mM effectively inhibited the respiratory activity of isolated rat liver mitochondria by uncoupling respiration and phosphorylation processes, induced depolarization of the mitochondrial membrane and potentiated Ca²⁺-stimulated formation of mitochondrial permeability transition pore in EGTA-free media. Cyclosporine A and ruthenium red partially inhibited the mitochondrial pore opening process induced by salicylic and acetylsalicylic acids both in the absence and in the presence of Ca²⁺ ions. Salicylic acid (180–360 μM) significantly accelerated proton-induced lysis (at pH 3.2) of human erythrocytes and caused hyperpolarization of erythrocyte membranes (at pH 5.5, but not at pH 7.4), probably as a result of proton transfer into the cytoplasm of the cell. Thus, salicylic and acetylsalicylic acids interact with mitochondrial and plasma membranes, act as effective proton/Ca²⁺ ionophores, and stimulate the mitochondrial calcium uniporter.

The formation of behavioral skills, consisting of the ability to learn the conditioned reaction of active avoidance, in different lines of rats in a three-way maze has been experimentally studied. To determine the most trained lines, white mongrel rats (100 individuals) and Long Evans and Dumbo rats (30 individuals each) were selected. The conditional stimulus was a combination of turning on a sound and turning off a light in a randomly selected target corridor of the maze. At 5 s after turning on the sound, the light was turned off, an unconditional stimulus (electric current) was supplied to the nontarget corridors and the light was turned on. The task of the rat was to make the transition to the target (safe) way of the maze in response to a sound stimulus. Upon reaching the target, the voltage was removed from the floor of the nontarget corridors and the lights were turned off. The pause between the combinations of conditional/unconditional stimulus was 30 s, the training time for each type of rat was 1 month with 20 presentations of combinations of stimuli per day. Each rat was considered trained with a probability of achieving the goal in 70% or more cases in a time not exceeding 6 s. It has been found that Dumbo rats were best suited for rapid training of large groups of rats to respond to an irritating stimulus.