Computational approach to design of aptamers to the receptor binding domain of sars-cov-2

The aim of the research. In this work, in silico selection of DNA-aptamers to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was performed using molecular modeling methods. Material and methods. A new computational approach to aptamer in silico selection is based on a cycle of simulations, including the stages of molecular modeling, molecular docking, molecular dynamic simulations, and quantum chemical calculations. To verify the obtained calculated results flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods were applied. Results. An initial library consisted of 256 16-mer oligonucleotides was modeled. Based on molecular docking results, the only one aptamer (Apt16) was selected from the library as a starting aptamer to the RBD protein. For Apt16/RBD complex, molecular dynamic and quantum chemical calculations revealed the pairs of nucleotides and amino acids whose contribution to the binding between aptamer and RBD is the largest. Taking into account these data, Apt16 was subjected to the structure modifications in order to increase the binding with the RBD. Thus, a new aptamer Apt25 was designed. The procedure of 1) aptamer structure modeling/modification, 2) molecular docking, 3) molecular dynamic simulations, 4) quantum chemical calculations was performed sev-eral times. As a result, four aptamers (Apt16, Apt25, Apt27, Apt31) to the RBD were designed in silico without any preliminary experimental data. Binding of the each modeled aptamer to the RBD was studied in terms of interactions between residues in protein and nucleotides in the aptamers. Based on the simulation results, the strongest binding with the RBD was predicted for two Apt27 and Apt31aptamers. The calculated results are in good agreement with experimental data obtained by flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods. Conclusion. The proposed computational approach to selection and refinement of aptamers is universal and can be used for wide range of molecular ligands and targets. Key words

Step-Wise Computational Synthesis of Fullerene C60 derivatives. 1.Fluorinated Fullerenes C60F2k

The reactions of fullerene C60 with atomic fluorine have been studied by unrestricted broken spin-symmetry Hartree-Fock (UBS HF) approach implemented in semiempirical codes based on AM1 technique. The calculations were focused on a sequential addition of fluorine atom to the fullerene cage following indication of the cage atom highest chemical susceptibility that is calculated at each step. The effectively-non-paired-electron concept of the fullerene atoms chemical susceptibility lays the foundation of the suggested computational synthesis. The obtained results are analyzed from energetic, symmetry, and the composition abundance viewpoints. A good fitting of the data to experimental findings proves a creative role of the suggested synthesis methodology.Comment: 33 pages, 11 figures, 2 tables, 2 chart

Mathematical Modeling of a Solar Arrays Deploying Process at Ground Tests

This paper focuses on the creating of a mathematical model of a solar array deploying process during ground tests. Lagrange equation was used to obtain the math model. The distinctive feature of this mathematical model is the possibility of taking into account the gravity compensation system influence on the construction in the deploying process and the aerodynamic resistance during ground tests

Picosecond Fluorescence Relaxation Spectroscopy of the Calcium-Discharged Photoproteins Aequorin and Obelin

Addition of calcium ions to the Ca2+-regulated photoproteins, such as aequorin and obelin, produces a blue bioluminescence originating from a fluorescence transition of the protein-bound product, coelenteramide. The kinetics of several transient fluorescent species of the bound coelenteramide is resolved after picosecond-laser excitation and streak camera detection. The initially formed spectral distributions at picosecond-times are broad, evidently comprised of two contributions, one at higher energy (25000 cm-1) assigned as from the Ca2+-discharged photoprotein-bound coelenteramide in its neutral state. This component decays much more rapidly (t1/2 2 ps) in the case of the Ca2+-discharged obelin than aequorin (t1/2 30 ps). The second component at lower energy shows several intermediates in the 150-500 ps times, with a final species having spectral maxima 19400 cm-1, bound to Ca2+-discharged obelin, and 21300 cm-1, bound to Ca2+-discharged aequorin, and both have a fluorescence decay lifetime of 4 ns. It is proposed that the rapid kinetics of these fluorescence transients on the picosecond time scale, correspond to times for relaxation of the protein structural environment of the binding cavit

Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming

Stem cells provide fascinating prospects for biomedical applications by combining the ability to renew themselves and to differentiate into specialized cell types. Since the first isolation of embryonic stem (ES) cells about 30 years ago, there has been a series of groundbreaking discoveries that have the potential to revolutionize modern life science. For a long time, embryos or germ cell-derived cells were thought to be the only source of pluripotency—a dogma that has been challenged during the last decade. Several findings revealed that cell differentiation from (stem) cells to mature cells is not in fact an irreversible process. The molecular mechanism underlying cellular reprogramming is poorly understood thus far. Identifying how pluripotency maintenance takes place in ES cells can help us to understand how pluripotency induction is regulated. Here, we review recent advances in the field of stem cell regulation focusing on key transcription factors and their functional interplay with non-coding RNAs

System of Forest Insect Pheromone Communication: Stability of «Information» Molecules to Environmental Factors

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.Features of external environmental factors (such as electromagnetic radiation in certain spectral bands) influencing pheromone molecules, which are carriers of information for forest insects in the search of the opposite sex, were examined. Stability of pheromone molecules for external influences has been studied for siberian moth Dendrolimus superans sibiricusTschetv., pine moth Dendrilimus piniL., gypsy moth Lymantria disparL., for xylophages Ips typographus L., Monochamus urussovi Fish. and Monochamus galloprovincialis Oliv. Properties of pheromone molecules were evaluated by calculations using quantum-chemical method B3LYP. Existing methods of quantum-chemical calculations are useful for analyzing the properties of quite small and uncomplicated molecules of forest insect pheromones. The calculations showed that the molecules of insect pheromones are able to absorb light in the ultraviolet range and move into an excited state. The values of dipole moments, the wavelengths of the absorption, atomic and molecular electronic properties of pheromones in the ground and excited states were calculated. The calculations showed that for the reaction of pheromones with oxygen an energy barrier is somewhat higher than for reactions of pheromones with water vapor. The worst reaction of pheromones with water molecules likely to pheromones such molecules whose dipole moment is comparable to the dipole moment of water. Quantum-chemical characteristics of the pheromone molecules can be linked to specific behavior of the insects

System of Forest Insect Pheromone Communication: Stability of «Information» Molecules to Environmental Factors

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.Features of external environmental factors (such as electromagnetic radiation in certain spectral bands) influencing pheromone molecules, which are carriers of information for forest insects in the search of the opposite sex, were examined. Stability of pheromone molecules for external influences has been studied for siberian moth Dendrolimus superans sibiricusTschetv., pine moth Dendrilimus piniL., gypsy moth Lymantria disparL., for xylophages Ips typographus L., Monochamus urussovi Fish. and Monochamus galloprovincialis Oliv. Properties of pheromone molecules were evaluated by calculations using quantum-chemical method B3LYP. Existing methods of quantum-chemical calculations are useful for analyzing the properties of quite small and uncomplicated molecules of forest insect pheromones. The calculations showed that the molecules of insect pheromones are able to absorb light in the ultraviolet range and move into an excited state. The values of dipole moments, the wavelengths of the absorption, atomic and molecular electronic properties of pheromones in the ground and excited states were calculated. The calculations showed that for the reaction of pheromones with oxygen an energy barrier is somewhat higher than for reactions of pheromones with water vapor. The worst reaction of pheromones with water molecules likely to pheromones such molecules whose dipole moment is comparable to the dipole moment of water. Quantum-chemical characteristics of the pheromone molecules can be linked to specific behavior of the insects

New method for calculations of nanostructure kinetic stability at high temperature

A new universal method is developed for determination of nanostructure kinetic stability (KS) at high temperatures, when nanostructures can be destroyed by chemical bonds breaking due to atom thermal vibrations. The method is based on calculation of probability for any bond in the structure to stretch more than a limit value Lmax, when the bond breaks. Assuming the number of vibrations is very large and all of them are independent, using the central limit theorem, an expression for the probability of a given bond elongation up to Lmax is derived in order to determine the KS. It is shown that this expression leads to the effective Arrhenius formula, but unlike the standard transition state theory it allows one to find the contributions of different vibrations to a chemical bond cleavage. To determine the KS, only calculation of frequencies and eigenvectors of vibrational modes in the groundstate of the nanostructure is needed, while the transition states need not be found. The suggested method was tested on calculating KS of bonds in some alkanes, octene isomers and narrow graphene nanoribbons of different types and widths at the temperature T=1200 K. The probability of breaking of the C–C bond in the center of these hydrocarbons is found to be significantly higher than at the ends of the molecules. It is also shown that the KS of the octene isomers decreases when the double C˭C bond is moved to the end of the molecule, which agrees well with the experimental data. The KS of the narrowest graphene nanoribbons of different types varies by 1–2 orders of magnitude depending on the width and structure, while all of them are by several orders of magnitude less stable at high temperature than the hydrocarbons and benzene

On the possibility of contact-induced spin polarization in interfaces of armchair nanotubes with transition metal substrates

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.The interaction between armchair carbon and boron nitride nanotubes (NT) with ferromagnetic transition metal (TM) surfaces, namely, Ni(111) and Co(0001), was studied by means of density functional theory. Different configurations of composite compartments mutual arrangement were considered. Partial densities of states and spin density spatial distribution of optimized structures were investigated. Influence of ferromagnetic substrate on nanotubes’ electronic properties was discussed. The values of spin polarization magnitude at the Fermi level are also presented and confirm the patterns of spin density spatial distribution