The model for high-performance molecular dynamics simulation of TiO2-SiO2-SiO2 thin films is proposed. This model allows us to consider both low-energy and high-energy thin film deposition processes. In connection with practical demands, special attention is paid to the properties of the transition regions between the TiO2 and SiO2 layers. It has been established that the concentration of some types of point defects in the transition region is approximately two times higher than in the depth of the layer. The effect of annealing on the concentration of defects is studied. A way to increase the computational efficiency of the modeling procedure is proposed.

The use of computer simulation methods has become an indispensable component in identifying drugs against the SARS-CoV-2 coronavirus. There is a huge body of literature on application of molecular modelling to predict inhibitors against target proteins of SARS-CoV-2. To keep our review clear and readable, we limited ourselves primarily to works that use computational methods to find inhibitors and test the predicted compounds experimentally either in target protein assays or in cell culture with live SARS-CoV-2. Some works containing results of experimental discovery of corresponding inhibitors without using computer modelling are included as examples of a success. Also, some computational works without experimental confirmations are also included if they attract our attention either by simulation methods or by databases used. This review collects studies that use various molecular modelling methods: docking, molecular dynamics, quantum mechanics, machine learning, and others. Most of these studies are based on docking, and other methods are used mainly for post-processing to select the best compounds among those found through docking. Simulation methods are presented concisely, information is also provided on databases of organic compounds that can be useful for virtual screening, and the review itself is structured in accordance with coronavirus target proteins.

Full-atomistic modeling of the deposition of TiO2, SiO2 and TiO2–SiO2 films is performed using parallel calculations. The dependence of film density on the deposition angle and deposition energy is studied. Simulation of post-deposition annealing of film structures is also carried out. Mechanical stresses in TiO2–SiO2 films, arising due to differences in the properties of silicon dioxide and titanium dioxide, are calculated. It is found that the film density decreases with decreasing deposition energy and increasing deposition angle. The use of surfacing annealing leads to an increase in film thickness. In two-layer TiO2–SiO2 films, the stresses are compressive. Particular attention is paid to reducing computational costs when simulating large atomistic clusters, consisting of hundreds of thousands of atoms. Reducing the parameter that determines the calculation of the electrostatic part of interatomic energy significantly reduces the simulation time. At the same time, in this case, the accuracy of determining the electrostatic energy in the reciprocal space decreases, which should be taken into account during modeling.

An atomistic simulation of silicon dioxide thin films deposited using oxide targets is performed. The influence of the oxide target on the deposition process is taken into account by introducing O=Si=O molecules into the flow of particles moving from the target to the substrate. The fraction of these molecules varied from 0 to 50%. It was found that the presence of O=Si=O molecules leads to film densification during a normal deposition. With a low-energy deposition, the increase in density was twice as high as with a high-energy deposition. The absolute value of the compressive stress increased with an increasing fraction of O=Si=O molecules in the flow of deposited particles at a normal, high-energy deposition. The influence of O=Si=O molecules on the structure of the glancing angle deposited films depends on the deposition angle.

Two solvent models, COSMO (old parametrization) and COSMO2 (new parametrization) are compared for a set of protein–ligand complexes in quantum quasi-docking, which is two-stage docking: positioning of a ligand in a target protein and calculation of binding enthalpy of the protein–ligand system using the PM7 quantum-chemical semiempirical method. In quantum quasi-docking, a wide spectrum of unique low-energy minima of the protein–ligand system is first found while employing the classical force field. Then energies of all these minima are recalculated within one of the continual models using the modern PM7 method with allowance for the solvent, and the global energy minimum is determined among the recalculated energies. The solution of the quantum quasi-docking problem is the position of the ligand in the protein corresponding to the global minimum of the protein–ligand system energy calculated by the quantum-chemical method with allowance for the solvent. Effectiveness of quantum quasi-docking is defined by the value (below 2 Å) of the root-mean-square deviation of ligand atoms from one another in two positions, namely, the position of the ligand in the protein corresponding to the calculated global energy minimum and the experimentally found crystallized position of the ligand with the protein. Comparison is performed for ten protein–ligand test complexes with well-defined structures taken from the Protein Data Bank, for which the ligand–protein binding enthalpy is measured and the positioning of the ligand in the protein is successful in quasi-docking within both solvent models used. In both methods, PM7 + COSMO and PM7 + COSMO2, a high correlation coefficient of the experimental and calculated ligand–protein binding enthalpy is obtained for both calculation techniques. Allowance for moveability of protein atoms in calculations of binding enthalpy leads to an increase in its negative values and to a slight decrease in the correlation coefficient of the experimental and calculated values. The role of hydrogen bonds between protein and ligand atoms is revealed: their contribution to binding enthalpy ranges from 14 to 24

The model for high-performance molecular dynamics simulation of TiO_2-SiO_2 thin films is proposed. This model allows us to consider both low-energy and high-energy thin film deposition processes. In connection with practical demands, special attention is paid to the properties of the transition regions between the TiO_2 and SiO_2 layers. It has been established that the concentration of some types of point defects in the transition region is approximately two times higher than in the depth of the layer. The effect of annealing on the concentration of defects is studied. A way to increase the computational efficiency of the modeling procedure is proposed.

Computer aided structural based approach was used to find inhibitors of SARS-CoV-2 nsp16 (2'-O-methyltransferase). Docking based virtual screening of three libraries, Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library, was performed. In total, 39350 3D-structures of low molecular weight ligands were docked into a model of nsp16 prepared using the structure of 6WKQ complex from the Protein Data Bank. Docking was performed by the SOL docking program. For the best SOL scored ligands, the protein-ligand binding enthalpy was calculated using the PM7 semiempirical quantum-chemical method with the COSMO implicit solvent model. The most promising eleven compounds were purchased and their inhibitory activity against the recombinant viral nsp16 protein was measured using MST assay with Monolith NT.115. As a result, two compounds, Z195979162 and Z1333277068, from Enamine Coronavirus Library demonstrated dissociation constants Kd for nsp16/nsp10 complex equal to 2.0 and 5.0 μM. The relative stability of these ligands in their docked positions in the nsp16 S-adenosylmethionine (SAM) binding site was confirmed in the molecular dynamics simulations along 70 ns trajectories. Z195979162 and Z1333277068 compounds belong to two chemical classes: 1,4-disubstituted tetrahydropyridines and derivatives of pyrazole-5-carboxamide, respectively, and can be good starting points for further hit optimization in the field of nsp16 inhibitors design.

The previously proposed method of molecular dynamics modelling for the sputter deposition of thin films from metal targets has been adapted for the case of dielectric targets and applied to silicon dioxide films. The possibility of the ejection from targets of not only silicon atoms but also clusters with oxygen atoms is taken into account by adding O=Si=O molecules to the flow of deposited atoms. Atomistic film clusters have been obtained at high-energy and low-energy sputter deposition with various percentages of molecules in the flow of deposited atoms. The values of the stress tensor components have been calculated. Compressive stresses are observed at high-energy deposition, while tensile stresses are observed at low-energy deposition. The absolute values of the diagonal components of the stress tensor increase with the increasing proportion of molecules in the flow of deposited atoms.

The model of large-scale molecular dynamics simulation of the deposition of the ZnO films is developed. The dependence of the films structure on the deposition angle is studied for the case of high-energy deposition. The formation of nanostructured films at large deposition angle is demonstrated. The numerical efficiency of the model is discussed.

The high-performance molecular dynamics simulation of the ion-assisted deposition of thin films is performed. The most time-consuming computational procedures are discussed. The structural parameters of the deposited films, depending on the deposition conditions, are calculated and verified using experimental data.

A systematic study of the most significant parameters of the ion-assisted deposited silicon dioxide films is carried out using the classical molecular dynamics method. The energy of the deposited silicon and oxygen atoms corresponds to the thermal evaporation of the target; the energy of the assisting oxygen ions is 100 eV. It is found that an increase in the flow of assisting ions to approximately 10% of the flow of deposited atoms leads to an increase in density and refractive index by 0.5 g/cm3 and 0.1, respectively. A further increase in the flux of assisting ions slightly affects the film density and density profile. The concentration of point defects, which affect the optical properties of the films, and stressed structural rings with two or three silicon atoms noticeably decrease with an increase in the flux of assisting ions. The film growth rate somewhat decreases with an increase in the assisting ions flux. The dependence of the surface roughness on the assisting ions flux is investigated. The anisotropy of the deposited films, due to the difference in the directions of motion of the deposited atoms and assisting ions, is estimated using the effective medium approach.

Ab initio molecular dynamics modeling in the NPT ensemble is used to obtain amorphous states by melting SiO2, ZrO2 and HfO2 crystals. A wide range of melt stabilization temperatures are used. Two types of SiO2 amorphous states are obtained. For melt temperatures below 4500 K, a perfect silica glass is obtained without any point defects. For melt temperatures above 4500 K, silica point defects such as threefold coordinated oxygen atoms, edge-sharing SiO4-tetrahedra, and others together with a wide range of Si-O-Si rings including 3-, and 4-membered rings appear. When the temperature of the melt exceeds the ZrO2 and Hf-O2 crystal melting point by 100 - 400 K, a sharp drop in the density of amorphous states is observed, accompanied by a decrease in atomic coordination, but this does not lead to the formation of defect states in the depth of the band gap of hafnium and zirconium dioxides.

A virtual structure-oriented screening of candidates for inhibitors of blood coagulation factor XIIa was carried out. This coagulation factor is one of the most promising therapeutic targets for the development of anticoagulants without disturbing normal hemostasis. The screening was carried out in the database of organic compounds of the Voronezh State University, consisting of more than 19 thousand molecules. At the first stage of virtual screening, ligands were positioned in the active center of factor XIIa using the SOL docking program. At the second stage, for the best ligands, the protein-ligand binding enthalpy was calculated using the MOPAC program and the PM7 quantum-chemical method, taking into account the solvent in the COSMO continuum model. All calculations were carried out using the supercomputing resources at Lomonosov Moscow State University. In total, more than 30 thousand ligand conformers are docked, and for more than 400 of the best of them, the protein-ligand binding enthalpy was calculated. 16 compounds are selected as the most promising candidates for subsequent in vitro testing of their ability to inhibit factor XIIa.

The article describes a method for the synthesis and evidence of the structure of new compounds of the class of 3-alkylsulfonyl-5-amino-1,2,4-triazoles. The inhibitory effect of the synthesized substances on copper corrosion in neutral and acidic chloride-containing media was evaluated using direct tests in a salt-spray chamber and weight loss measurements as well as potentiodynamic polarization measurements. It has been established that some of the studied compounds can be highly effective copper corrosion inhibitors under the studied conditions. The degree of protection increases with increasing inhibitor concentration. The results of tests in an acidic chloride environment generally correlate with the corresponding experiments in neutral aqueous solutions. The highest degree of protection was obtained for 3 -butylsulphonyl-5-amino-1H-1,2,4-triazole, 3-benzylsulphonyl-5-amino-1H-1,2,4-triazole and 3-phenethyl-sulphonyl-5-amino-1H-1,2,4-triazole at a concentration of 1.00 mM, as well as for 3-propylsulphonyl-5-amino-1H-1,2,4-triazole at a concentration of 0.01 mM. Despite the low degrees of protection in acidic solutions, 3-pentylsulphonyl-5-amino-1H-1,2,4-triazole and 3-nonylsulphonyl-5-amino-1H-1,2,4-triazole were found to be very effective in protecting copper from atmospheric corrosion based on experiments in a salt spray chamber. This result is probably achieved due to the formation of a surface film of the inhibitor, which is characterized by high hydrophobicity, and therefore prevents physical contact of the salt fog with the metal.

Docking and quantum-chemical methods have been used for screening of drug-like compounds from the own database of the Voronezh State University to find inhibitors the SARS-CoV-2 main protease, an important enzyme of the coronavirus responsible for the COVID-19 pandemic. Using the SOL program more than 42000 3D molecular structures were docked into the active site of the main protease, and more than 1000 ligands with most negative values of the SOL score were selected for further processing. For all these top ligands, the protein-ligand binding enthalpy has been calculated using the PM7 semiempirical quantum-chemical method with the COSMO implicit solvent model. 20 ligands with the most negative SOL scores and the most negative binding enthalpies have been selected for further experimental testing. The latter has been made by measurements of the inhibitory activity against the main protease and suppression of SARS-CoV-2 replication in a cell culture. The inhibitory activity \of the compounds was determined using a synthetic fluorescently labeled peptide substrate including the proteolysis site of the main protease. The antiviral activity was tested against SARS-CoV-2 virus in the Vero cell culture. Eight compounds showed inhibitory activity against the main protease of SARS-CoV-2 in the submicromolar and micromolar ranges of the IC50 values. Three compounds suppressed coronavirus replication in the cell culture at the micromolar range of EC50 values and had low cytotoxicity. The found chemically diverse inhibitors can be used for optimization in order to obtain a leader compound, the basis of new direct-acting antiviral drugs against the SARS-CoV-2 coronavirus.

Docking and quantum-chemical methods have been used for screening of drug-like compounds from the own database of the Voronezh State University to find inhibitors the SARS-CoV-2 main protease, an important enzyme of the coronavirus responsible for the COVID-19 pandemic. Using the SOL program more than 42000 3D molecular structures were docked into the active site of the main protease, and more than 1000 ligands with most negative values of the SOL score were selected for further processing. For all these top ligands, the protein-ligand binding enthalpy has been calculated using the PM7 semiempirical quantum-chemical method with the COSMO implicit solvent model. 20 ligands with the most negative SOL scores and the most negative binding enthalpies have been selected for further experimental testing. The latter has been made by measurements of the inhibitory activity against the main protease and suppression of SARS-CoV-2 replication in a cell culture. The inhibitory activity \of the compounds was determined using a synthetic fluorescently labeled peptide substrate including the proteolysis site of the main protease. The antiviral activity was tested against SARS-CoV-2 virus in the Vero cell culture. Eight compounds showed inhibitory activity against the main protease of SARS-CoV-2 in the submicromolar and micromolar ranges of the IC50 values. Three compounds suppressed coronavirus replication in the cell culture at the micromolar range of EC50 values and had low cytotoxicity. The found chemically diverse inhibitors can be used for optimization in order to obtain a leader compound, the basis of new direct-acting antiviral drugs against the SARS-CoV-2 coronavirus.

Anisotropy of SiO2 films fabricated by glancing angle deposition is investigated using the classical atomistic simulation and anisotropic Bruggeman effective medium theory. The voids between the slanted columns, occurring as a result of glancing angle deposition, are considered as ellipsoids. Averaged shape parameters of these ellipsoids are defined using the density gradient tensor. Calculated values of difference of refractive index components of glancing angle deposited SiO2 films are in accordance with experiment.

The previously developed large-scale molecular dynamics approach is applied to high-performance parallel modelling the deposition of TiO2 thin films. The largest simulated clusters reach 40 nm in size with about two million atoms. The surface roughness and porosity of normally deposited films with a flux of high and low energy atoms for cold and hot substrates are investigated. The formation of separate nanostructures in high-energy glancing angle deposited films is studied. The averaged structural parameters of the elongated pores in these films are determined using the original Monte Carlo based method. The difference between the main components of the refractive index tensor of glancing angle deposited TiO2 thin films is calculated.

The classical molecular dynamics simulation of the low-energy glancing angle deposition of titanium dioxide films is performed. The deposition angle varies from 60° to 80°. It is found that the film structure consists of parallel slanted columns which lead to the anisotropy of films properties. The difference between the main components of the refractive index tensor is about 0.14, which is close to the values obtained for high-energy titanium dioxide films and larger than 0.03 obtained earlier for silicon dioxide films.

Disorders in the blood coagulation system are the leading cause of death and disability in the modern world. So the search for new drugs that can prevent pathological thrombosis, while not affecting normal hemostasis, becomes more relevant than ever. Recent studies has been a revolution in the understanding of the principles of work and the regulation of blood coagulation. In addition, new, more effective approaches to drug development have now appeared. For example computer simulation methods that can significantly reduce the time and resources spent on the search for new candidate molecules. In the review, the blood clotting system, the molekular mechanisms of thrombosis, the role of blood coagulation factors Xa and XIa, and the urgency of developing new inhibitors of these targets are shown, and the most interesting inhibitors of factors Xa and XIa are presented.