Yuri Porozov

• M.D., Ph.D.
• Head of the laboratory at HSE University

The use of the concept of privileged structures significantly accelerates the search for new leads and their optimization. 6-(methylsulfonyl)-8-(4-methyl-4H-1,2,4-triazol-3-yl)-2-(5-nitro-2-furoyl)-2,6-diazaspiro[3.4]octane 1 has been identified as a lead, with MICs of 0.0124–0.0441 μg/mL against MTb multiresistant strains. Several series of struct...

The Dicer protein is an indispensable player in such fundamental cell pathways as miRNA biogenesis and regulation of protein expression in a cell. Most recently, both germline and somatic mutations in DICER1 have been identified in diverse types of cancers, which suggests Dicer mutations can lead to cancer progression. In addition to well-known hot...

The annual number of reported human cases of flavivirus infections continues to increase. Measures taken by local healthcare systems and international organizations are not fully successful. In this regard, new approaches to treatment and prevention of flavivirus infections are relevant. One promising approach is to use monoclonal antibody preparat...

A series of 13 new 3-substituted 5-(5-nitro-2-furyl)-1,2,4-oxadiazoles was synthesized from different aminonitriles. All compounds were screened in the disc diffusion test at a 100 μg/mL concentration to determine the bacterial growth inhibition zone presence and diameter, and then the minimum inhibitory concentrations (MICs) were determined for th...

Despite the development of numerous advanced ligands for Pd-catalyzed Suzuki cross-coupling reactions, the potential of (oligo)peptides serving as ligands has remained largely unexplored. This study demonstrates, via DFT modeling, that (oligo)peptide ligands can exhibit superior activity compared to classic phosphines in these reactions. The utiliz...

Despite the development of numerous advanced ligands for Pd-catalyzed Suzuki cross-coupling reactions, the potential of (oligo)peptides serving as ligands has remained largely unexplored. This study demonstrates, via DFT modeling, that (oligo)peptide ligands can exhibit superior activity compared to classic phosphines in these reactions. The utiliz...

Over the past decades, the problem of bacterial resistance to most antibiotics has become a serious threat to patients' survival. Nevertheless, antibiotics of a novel class have not been approved since the 1980s. The development of antibiotic potentiators is an appealing alternative to the challenging process of searching for new antimicrobials. Pr...

A novel method for synthesizing 1,2,4-triazole- and tetrazole-containing 4H-thiopyrano[2,3-b]quinolines using a new combination of the thio-Michael and aza-Morita–Baylis–Hillman reactions was developed. Target compounds were evaluated for their cytotoxicities and antiviral activities against influenza A/Puerto Rico/8/34 virus in MDCK cells. The com...

Prediction of catalytic reaction efficiency is one of the most intriguing and challenging applications of machine learning (ML) algorithms in chemistry. In this study, we demonstrated a strategy for utilizing ML protocols applied to Quantum Theory of Atoms In Molecules (QTAIM) parameters to predict the ability of the A17 L47K catalytic antibody to...

Dopamine receptor D3 (D3R) has gained attention as a promising therapeutic target for neurological disorders. In this study, an innovative in silico click reaction strategy was employed to identify potential D3R binders. The ligand template, 1-phenyl-4-[4-(1H-1,2,3-triazol-5-yl)butyl]piperazine, with substitution at the 1,2,3-triazole ring, served...

Antipsychotic drugs, also known as neuroleptics, are commonly used to treat psychosis associated with schizophrenia and bipolar disorder. The effectiveness of these drugs largely depends on their ability to permeate the blood-brain barrier (BBB) and interact with drug receptors (pharmacokinetics and pharmacodynamics). In this study, we developed an...

Bacteria have evolved a sophisticated array of signal transduction systems that allow them to adapt their physiology and metabolism to changing environmental conditions. Typically, these systems recognize signals through dedicated ligand binding domains (LBDs) to ultimately trigger a diversity of physiological responses. Nonetheless, an increasing...

Since the beginning of the COVID-19 pandemic, whole-genome sequences of SARS-CoV-2 have been continuously added to public databases, such as NCBI Virus [4] and GISAID [3].

The aim of this work was to design and characterize peptides based on the α-helices h1 and h2 of the ACE2 receptor, forming the interaction interface between the receptor-binding domain (RBD) of the SARS-CoV-2 S protein and the cellular ACE2 receptor. Monomeric and heterodimeric peptides connected by disulfide bonds at different positions were synt...

Flaviviruses are single-stranded RNA viruses that have emerged in recent decades and infect up to 400 million people annually, causing a variety of potentially severe pathophysiological processes including hepatitis, encephalitis, hemorrhagic fever, tissues and capillaries damage. The Flaviviridae family is represented by four genera comprising 89...

a smirnav 2@mail.ru Corresponding author: A.V. Smirnov, smirnav 2@mail.ru PACS 61.05.cf, 71.15. Pd, 87.15.B-ABSTRACT The SASPAR program for calculation of SAXS of proteins in solution uses trajectories of molecular dynamics (MD) and an explicit solvent model. The program allows one to take into account real interactions of solvent molecules both be...

Inhibition of human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) by different chiral lipophilic nucleoside derivatives was studied. New Tdp1 inhibitors were found in the series of the studied compounds with IC50 = 2.7–6.7 μM. It was shown that D-lipophilic nucleoside derivatives manifested higher inhibition activity than their L-analogs...

During the COVID-19 pandemic, genomics and bioinformatics have emerged as essential public health tools. The genomic data acquired using these methods have supported the global health response, facilitated the development of testing methods and allowed the timely tracking of novel SARS-CoV-2 variants. Yet the virtually unlimited potential for rapid...

Compounds that contain (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid substituted with bicyclic amino moiety (2-aza-bicyclo[2.2.1]heptane) were designed using molecular modelling methods, synthesised, and found to be potent DPP-4 (dipeptidyl peptidase-4) inhibitors. Compound 12a (IC50 = 16.8 ± 2.2 nM), named neogliptin, is a more potent DPP-4 i...

PCSK9 has now become an important target to create new classes of lipid-lowering drugs. The prevention of its interaction with LDL receptors allows an increase in the number of these receptors on the surface of the cell membrane of hepatocytes, which leads to an increase in the uptake of cholesterol-rich atherogenic LDL from the bloodstream. The PC...

Myelodysplastic syndrome (MDS) refers to a heterogeneous group of closely related clonal hematopoietic disorders, which are characterized by accumulation of somatic mutations. The acquired mutation burden is suggested to define the pathway and consequent phenotype of the pathology. Recent studies have called attention to the role of miRNA biogenesi...

Fluorescently labeled nanoparticles are widely used for evaluating their distribution in the biological environment. However, dye leakage can lead to misinterpretations of the nanoparticles’ biodistribution. To better understand the interactions of dyes and nanoparticles and their biological environment, we explored PLGA nanoparticles labeled with...

In this article, we present our novel pipeline for analysis of metabolic activity using a microbial community's metatranscriptome sequence data set for validation. Our method is based on expectation-maximization (EM) algorithm and provides enzyme expression and pathway activity levels. Further expanding our analysis, we consider individual enzymati...

Rapidly evolving RNA viruses continuously produce minority haplotypes that can become dominant if they are drug-resistant or can better evade the immune system. Therefore, early detection and identification of minority viral haplotypes may help to promptly adjust the patient's treatment plan preventing potential disease complications. Minority hapl...

The difference in symbiotic specificity between peas of Afghanistan and European phenotypes was investigated using molecular modeling. Considering segregating amino acid polymorphism, we examined interactions of pea LykX-Sym10 receptor heterodimers with four forms of Nodulation factor (NF) that varied in natural decorations (acetylation and length...

More than any other infectious disease epidemic, the COVID-19 pandemic has been characterized by the generation of large volumes of viral genomic data at an incredible pace due to recent advances in high-throughput sequencing technologies, the rapid global spread of SARS-CoV-2, and its persistent threat to public health. However, distinguishing the...

More than any other infectious disease epidemic, the COVID-19 pandemic has been characterized by the generation of large volumes of viral genomic data at an incredible pace due to recent advances in high-throughput sequencing technologies, the rapid global spread of SARS-CoV-2, and its persistent threat to public health. However, distinguishing the...

ABSTARCT The development of new anti-influenza drugs remains an active area, and efforts in this direction will likely continue far into the future. In this paper, we present the results of a theoretical study explaining the mechanisms behind the antiviral activity of camphor derivatives. These include camphecene and a number of its analogues. The...

Investigation of the influence of molecular structure of different organic compounds on acute toxicity towards Fathead minnow, Daphnia magna, and Tetrahymena pyriformis has been carried out using 2D simplex representation of molecular structure and two modelling methods: Random Forest (RF) and Gradient Boosting Machine (GBM). Suitable QSAR (Quantit...

The difference in symbiotic specificity between peas of Afghanistan and European phenotypes was interrogated using molecular modeling. Considering segregating amino acid polymorphism, we examined interactions of pea LykX-Sym10 receptor heterodimers with four forms of Nod factor (NF) that varied in natural decorations (acetylation and length of the...

The investigation of influence of the molecular structure of different organic compounds on acute, developmental toxicity, mutagenicity has been carried out with the usage of 2D simplex representation of molecular structure and Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Machine (GBM), Partial Least Squares (PLS). Suitable Q...

Na,K-ATPase is a redox-sensitive transmembrane protein. Understanding the mechanisms of Na,K-ATPase redox regulation can help to prevent impairment of Na,K-ATPase functioning under pathological conditions and reduce damage and death of cells. One of the basic mechanisms to protect Na,K-ATPase against stress oxidation is the glutathionylation reacti...

The kidney is essential for systemic calcium homeostasis. Urinary calcium excretion can be viewed as an integrative renal response to endocrine and local stimuli. The extracellular calcium-sensing receptor (CaSR) elicits a number of adaptive reactions to increased plasma Ca2+ levels including the control of parathyroid hormone release and regulatio...

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting a variety of hydrophobic ligands, including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth, which can be attributed to its estrogen-binding ability. Despite AFP having long been investigated, its three-d...

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimen...

Transitions between different conformational states are ubiquitous in proteins. A vast class of conformation-changing proteins includes evolutionary switches, which vary their conformation as an effect of few mutations or weak environmental variations. However, modeling those processes is extremely difficult due to the need of efficiently exploring...

Transitions between different conformational states are ubiquitous in proteins, being involved in signaling, catalysis, and other fundamental activities in cells. However, modeling those processes is extremely difficult, due to the need of efficiently exploring a vast conformational space in order to seek for the actual transition path for systems...

In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients’ prognosis. It was widely demonstrated that...

Oxidative stress is a consequence of the use of oxygen in aerobic respiration by living organisms and is denoted as a persistent condition of an imbalance between the generation of reactive oxygen species (ROS) and the ability of the endogenous antioxidant system (AOS) to detoxify them. The oxidative stress theory has been confirmed in many animal...

Oxidative stress is a consequence of the use of oxygen in aerobic respiration by living organisms and is denoted as a persistent condition of an imbalance between the generation of reactive oxygen species (ROS) and the ability of the endogenous antioxidant system (AOS) to detoxify them. The oxidative stress theory has been confirmed in many animal...

Transitions between different conformational states are ubiquitous in proteins, being involved in signaling, catalysis and other fundamental activities in cells. However, modeling those processes is extremely difficult, due to the need of efficiently exploring a vast conformational space in order to seek for the actual transition path for systems w...

Taxifolin, also known as di­hydro­quercetin, is the major flavonoid in larch wood. It is well known as an antioxidant and a bioactive substance. Taxifolin as an active pharmaceutical ingredient is produced industrially in crystalline form during the processing of larch wood. Some information is available on nano- and microstructured particles of ta...

Flavonoid-mediated materials are promising substances for the design of new functional materials because of their bioactivity, eco-friendliness, and cost-effectiveness. Dihydroquercetin (DHQ) is the major flavonoid in the wood of Larix dahurica Turcz. Previously some new modifications were created on the basis of DHQ, they were characterized by dif...

Novel palladium(II) and platinum(II) complexes (trans-[PdCl2L2] and trans-[PtCl2L2] {L = 2-(5-methyl-1H-tetrazol-1-yl)acetamide, N-(sec-butyl)-2-(5-methyl-1H-tetrazol-1-yl)acetamide, N-cyclopropyl-2-(5-methyl-1H-tetrazol-1-yl)acetamide, N-cyclohexyl-2-(5-methyl-1H-tetrazol-1-yl)acetamide, 2-(2-(tert-butyl)-2H-tetrazol-5-yl)acetamide and 2-(2-(tert-...

Main conclusion: The LysM receptor-like kinase K1 is involved in regulation of pea-rhizobial symbiosis development. The ability of the crop legume Pisum sativum L. to perceive the Nod factor rhizobial signals may depend on several receptors that differ in ligand structure specificity. Identification of pea mutants defective in two types of LysM re...

Our goal is to reproduce one of possible approaches for in silico binding site prediction problem described at DeepSite paper [1]. We follow the original protocol and add several simplifications. Our ultimate goal is to reproduce given approach as close as possible and to compare results, to interpret network layers outputs and to experiment with m...

Sandwich-like docking configurations of the heterodimeric complex of NFR5 and K1 Vicia sativa receptor-like kinases together with the putative ligand, Nod factor (NF) of Rhizobium leguminosarum bv. viciae, were modeled and two of the most probable configurations were assessed through the analysis of the mutual polymorphisms and conservatism. We car...

Highly mutable RNA viruses such as influenza A virus, human immunodeficiency virus and hepatitis C virus exist in infected hosts as highly heterogeneous populations of closely related genomic variants.

Two series of palladium(II) and platinum(II) complexes featuring esters of tetrazol-1-yl and tetrazol-5-ylacetic acids {trans- [PdCl2L2] and trans-[PtCl2L2], L = 5-methyl-1H-tetrazol-1-ylacetic acid and its ethyl, butyl, iso-butyl esters (1-5); 2-R-2H-tetrazol-5-ylacetic acid and its ethyl esters, R = tBu, CH2CH2OH (6-10)} were synthesized and thei...

A growing body of evidence suggests that peptides may possess analgesic effects without tolerance development. The synthetic tetrapeptide Tyr-D-Arg-Phe-Gly-NH2 was modified with the inclusion of a (D-Arg)8 vector to prevent the action of endopeptidase and to increase the duration of the analgesic action of the tetrapeptide when administered orally....

Toll-Like Receptor 4 (TLR4) signal pathway plays an important role in initiating the innate immune response and its activation by bacterial endotoxin is responsible for chronic and acute inflammatory disorders that are becoming more and more frequent in developed countries. Modulation of the TLR4 pathway is a potential strategy to specifically targ...

We introduce a new way of modeling conformational movement of multi chain proteins. Several approaches for placing virtual bonds between the chains of proteins were tested. The first one simply connects the first atoms of all chains. The second approach is based on placing the virtual bonds between the most stable parts of the protein. The algorith...

A “coarse-grained” model of protein conformational mobility is presented. The conformational paths in five proteins, predicted using the model, are compared with those obtained by the nearest-neighbor method basing on the small-angle X-ray scattering data. The sequences of conformations evaluated with the help of these two approaches have been show...

The "coarse-grained" model of protein conformational mobility is presented. We compared the trajectories of conformational motions predicted for five proteins using this model with the motion obtained by the method of the "nearest neighbor", based on small-angle X-ray scattering data. It is shown that for all studied proteins the sequence of confor...

Succinic semialdehyde dehydrogenase (SSADH) converts succinic semialdehyde (SSA) to succinic acid in the mitochondrial matrix and is involved in the metabolism of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). The molecular structure of human SSADH revealed the intrinsic regulatory mechanism - redox-switch modulation - by which large c...

The problem of protein conformation motion model-ing is an open problem in the structural computational biology. It is difficult to solve it using methods of molecular dynamics or quantum physics because these methods deal with time intervals of nanoseconds or microseconds, while conformation motions take time of millisecond order. In addition, the...

Bio-inspired nano-communication enables nanoscale devices to exchange information with each other by various natural mechanisms of data transfer. One of the most perspective way in bio-inspired communications is using the protein interactions, which refer from various proteins conformation states. In this paper, we describe our new coarse-grained m...

Recent progress in metagenomics resulted in rapid accumulation of data on genetic diversity of microorganisms. This diversity is mostly represented by uncultured microorganisms, never described in regard to phenotype. Therefore, former phenotypic classification system of bacteria came out to be inapplicable to metagenomics and was thus replaced wit...

The paper highlights approaches to fast prediction of protein conformational mobility. A new mathematical model based on the transportation principle is proposed. We describe an algorithm and soft-ware developed for a construction of the possible trajectories of the large-scale conformational motions of proteins (i.e. movements that occur within re...

There are a number of methods for protein conformational mobility simulation including methods based on molecular dynamics and elastic networks. However, most of them are not applicable to large-scale motion modelling. The method based on the coarse-grained protein representation and the mass-transportation principle is proposed for that purpose.

In nature, the degradation of plant biomass, which mostly consists of plant cell walls, is implemented by microorganisms synthesizing cellulase class enzymes (CCEs). Cell walls fibers are composed of complex of polysaccharides, which is split by complicated CCEs. CCEs contain two types of domains. The first type is the catalytic domains that decomp...

The goals and objectives of some topics of structural bioinformatics are presented in the article. The main methods and approaches used in computer biology are highlighted. Areas in which bioinformatic science can greatly facilitate and speed up the work of practical biologist and pharmacologist are revealed. The features of both the basic packages...

In this study, an analysis of nucleotide and amino�acid polymorphisms in the receptor part of the nfr5 gene was conducted in 15 plants of the conjugate collection (Melilotus albus was the plant component; Sinorhizobium meliloti was the bacterial component). The domain structure of the studied region was determined and it was demonstrated that the m...

Modern databases and search engines for structural biology are very sophisticated and versatile. Ho wever, scientific life discovers new research topics almost every day. For instance scientific visualizat ion is a field where distances between different conformations play a crucial ro le. In our research of protein motions we have faced a problem...

Motivations. The vast majority of proteins and other biological macromolecules act in life processes through some form of motion. While this concept has been recognized and is ever more considered in the structural biology field, it is still difficult to handle by the majority of experimental scientists. We reasoned that a simple system that enable...

In the present work a molecular genetic analysis of the receptor part of the nfr5 gene in 15 plants of the conjugate collection (the plant component Melilotus albus, the bacterial component Sinorhizobium meliloti) has been done. Was studied the LysM domains structure and found a high level of the nucleotide polymorphism in LysM domains of this gene...

A systematicity in taxonomy, basically related to evolution, remains one of the greatest problem of in modern biology, and in particular microbiological topology. This problem has always attracted the attention of scientists, including N.I. Vavilov. He proposed a law of homologous series which, of course, must be regarded as the most striking in th...

Background / Purpose: At present, protein structural biology has several modeling methods for macromolecular conformational motions. In this work, we introduce and implement a new modeling method for predicting the conformational motion of protein molecules, whereby a protein is represented as a graph whose nodes mark the atoms of the backbone ch...

In this and the associated article 'BioBlender: A Software for Intuitive Representation of Surface Properties of Biomolecules', (Andrei et al) we present BioBlender as a complete instrument for the elaboration of motion (here) and the visualization (Andrei et al) of proteins and other macromolecules, using instruments of computer graphics. A vast n...

Cardiac and neuronal G protein-activated K+ channels (GIRK; Kir3) open following the binding of Gβγ subunits, released from Gi/o proteins activated by neurotransmitters. GIRKs also possess basal activity contributing to the resting potential in neurons. It appears to depend largely on free Gβγ, but a Gβγ-independent component has also been envisage...

Cardiac and neuronal G protein-activated K+ channels (GIRK; Kir3) open following the binding of Gβγ subunits, released from Gi/o proteins activated by neurotransmitters. GIRKs also possess basal activity contributing to the resting potential in neurons. It appears to depend largely on free Gβγ, but a Gβγ-independent component has also been envisage...

G protein-activated K(+) channels (GIRKs; Kir3) are activated by direct binding of Gbetagamma subunits released from heterotrimeric G proteins. In native tissues, only pertussis toxin-sensitive G proteins of the G(i/o) family, preferably Galpha(i3) and Galpha(i2), are donors of Gbetagamma for GIRK. How this specificity is achieved is not known. Her...

A method of rat heart isolation is described. A comprehensive description is given of the apparatus to record the contractile activity of spontaneously beating heart, which makes it possible to synchronize irradiation of the heart by the low-intensity laser light with the cardiac cycle phases.

In experiments on isolated amphibian hearts changes in photoreactivity of pacemaker cells under the influence of He-Ne laser radiation in different phases of the heart cycle were studied. The specificity of heart photoreaction, peculiarities of relaxation period after laser light action and laser modification of hypodynamic depression development w...