A5101695175- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Synthesis and biological activity
- thermodynamics and calorimetric analyses
- SARS-CoV-2 and COVID-19 Research
- Enzyme function and inhibition
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Spectroscopy and Quantum Chemical Studies
- Blood Coagulation and Thrombosis Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Advanced Chemical Physics Studies
- Tensor decomposition and applications
- Cholinesterase and Neurodegenerative Diseases
- Theoretical and Computational Physics
- Metabolomics and Mass Spectrometry Studies
- Advanced Differential Geometry Research
- Vitamin K Research Studies
- Protein Degradation and Inhibitors
- Ion-surface interactions and analysis
- Glass properties and applications
- Metal and Thin Film Mechanics
- Elasticity and Wave Propagation
- Matrix Theory and Algorithms
- Genetics, Bioinformatics, and Biomedical Research
Lomonosov Moscow State University
2015-2024
Institute of Mathematical Problems of Biology
2010-2024
Bauman Moscow State Technical University
2018-2023
Moscow Center For Continuous Mathematical Education
2021-2022
Sevastopol National Technical University
2021
Belarusian State University
2021
Moscow State University
2019
Marine Hydrophysical Institute
2016
Institute of Numerical Mathematics
2015
This paper is devoted to results obtained by the docking program SOL and post-processing DISCORE at CSAR benchmark. programs are described. original developed on basis of genetic algorithm, MMFF94 force field, rigid protein, precalculated energy grid including desolvation in frame simplified GB model, vdW, electrostatic interactions taking into account ligand internal strain energy. An important feature single- or multi-processor performance for up hundreds CPUs. improves binding scoring...
The adequate choice of the docking target function impacts accuracy ligand positioning as well protein-ligand binding energy calculation. To evaluate a we compared positions its minima with experimentally known pose in protein active site. We evaluated five functions based on either MMFF94 force field or PM7 quantum-chemical method without implicit solvent models: PCM, COSMO, and SGB. Each was tested same set 16 complexes. For exhaustive low-energy search novel MPI parallelized program FLM...
Results of the combined use classical force field and recent quantum chemical PM7 method for docking are presented. Initially gridless a flexible low molecular weight ligand into rigid target protein is performed with energy function calculated in MMFF94 implicit water solvent PCM model. Among several hundred thousand local minima, which found procedure, about eight lowest minima chosen then energies these recalculated semiempirical method. This procedure applied to 16 test complexes...
In consequence of the key role factor Xa in clotting cascade and absence its activity processes that do not affect coagulation, this protein is an attractive target for development new blood coagulation inhibitors. Factor more effective convenient creation anticoagulants than thrombin, inhibition which may cause some side effects. This study aimed at finding inhibitors by molecular computer modeling including docking SOL postdocking optimization DISCORE programs. After validation methods on...
We present the surface generalized born (S-GB) method, based on expansion of energy in a integral series. The method can be parametrized for simultaneous reproduction reaction field small molecules as well macromolecules. For set 195 molecules, our S-GB model gives root mean square (rms) 0.13 kcal/mol relative to rigorous polarizable continuum (PCM).
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 literature on application molecular modelling to predict inhibitors target proteins SARS-CoV-2. To keep our review clear and readable, we limited ourselves primarily works that computational find test predicted compounds experimentally either protein assays or cell culture with live Some containing results experimental discovery...
The previously developed high-performance method of the atomistic simulation thin film deposition is applied to investigation effects connected with SiO2 films annealing. It found that density reduced for about 0.15 g/cm3 under annealing temperature 1300 K. This corresponds reduction refractive index approximately 0.03. Concentrations non-bridging and threefold coordinated oxygen atoms are up four times after stress value essentially reduces at K thickness increases 3 nm.
The molecular dynamic algorithm for simulation of thin-film growth is reported. achieved performance this sufficient detailed investigations structural effects in thin films with practically meaningful dimensions.
Coagulation factor Xa and XIa are proven to be convenient crucial protein targets for treatment thrombotic disorders thereby their inhibitors can serve as effective anticoagulant drugs. In the present work, we focused on structure–activity relationships of derivatives pyrrolo[3,2,1-ij]quinolin-2(1H)-one an evaluation activity against XIa. For this, docking-guided synthesis nine compounds based was carried out. new hybrid hydropyrrolo[3,2,1-ij]quinolin-2(1H)-one derivatives, used structural...
In the modern world, complications caused by disorders in blood coagulation system are found almost all areas of medicine. Thus, development new, more advanced drugs that can prevent pathological conditions without disrupting normal hemostasis is an urgent task. The factor XIIa one most promising therapeutic targets for anticoagulants based on its inhibitors. initial stage drug directly related to computational methods searching a lead compound. this study, docking followed quantum chemical...
Urokinase-type plasminogen activator (uPA) plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, shortened survival patients, whereas suppression proteolytic activity leads to evident decrease metastasis. Therefore, been considered as a promising molecular target for development anticancer drugs. The present study sets out develop new selective...
A new method for supercomputer atomistic modeling of the ion beam sputtering process is presented allowing systems consisting 10<sup>6</sup> – 10<sup>8</sup> atoms. Deposition organized as a sequence molecular dynamic cycles in which deposited atoms interact with substrate earlier and form chemical bonds. The applied to SiO<sub>2</sub> thin optical films. For interatomic potential energy calculation original DESIL force field high computational efficiency has been developed. Atomistic...
Despite extensive research in the field of thrombotic diseases, prevention blood clots remains an important area study. Therefore, development new anticoagulant drugs with better therapeutic profiles and fewer side effects to combat thrombus formation is still needed. Herein, we report synthesis evaluation novel pyrroloquinolinedione-based rhodanine derivatives, which were chosen from 24 developed derivatives by docking as potential molecules inhibit clotting factors Xa XIa. For hybrid...
We present the novel docking algorithm based on Tensor Train decomposition and TT-Cross global optimization. The is applied to problem with flexible ligand moveable protein atoms. energy of protein-ligand complex calculated in frame MMFF94 force field vacuum. grid precalculated potentials probe atoms target not used. for any given configuration computed directly without fitting parameters. conformation space system coordinates formed by translations rotations as a whole, torsions also...
The initial step of the rational drug design pipeline extremely needs an increase in effectiveness. This can be done using molecular modeling: docking and dynamics. Docking programs are popular now due to their simple idea, quickness ease use. Nevertheless accuracy these still leaves much desired discovery by chance experimental screening play important role. performs ligand positioning target protein estimates protein-ligand binding free energy. While many cases is satisfactory, energy...
The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, virus responsible for pandemic, can be targeted in several ways. One of them inhibit 2'-O-methyltransferase (nsp16) enzyme that crucial effective translation viral RNA replication. For methylation substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding small molecule protein site where SAM binds disrupt synthesis proteins and, as result,...
Candidates to being inhibitors of the main protease (Mpro) SARS-CoV-2 were selected from database Voronezh State University using molecular modeling. The contained approximately 19,000 compounds represented by more than 41,000 ligand conformers. These ligands docked into Mpro SOL docking program. For one thousand with best values score, protein-ligand binding enthalpy was calculated PM7 quantum-chemical method COSMO solvent model. Using score and enthalpies, eighteen for experiments. Several...
Eectiveness of modern rational new drugs development is connected with accurate modelling binding between target-proteins responsible for the disease and small molecules (ligands) candidates to become drugs.The main modeling tools are docking programs positioning ligands in target proteins.Ligand realized frame paradigm: ligand binds protein pose corresponding global energy minimum on complicated multidimensional surface protein-ligand system.Docking algorithm base novel method tensor train...