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

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

Organizational conflicts during universities transformation: Destruam et aedificabo

Introduction. The authors tackle the topical problem of assessing the conflict level between subidentical groups: “management academics” (professors and lectures staff) and “academic managers” (administrative managing staff). The aim of the paper is to construct a new method of quantitative assessment of the conflict level between professional groups generated by the organizational culture; to study the dynamics of the change in the conflict level between professional and age-based cohorts existing in Russian universities. Materials and Methods. In this study, the conflict level is defined as a difference of common cultural vectors found for each of target age-groups, demonstrating generations' behavioral features and their professional competence, set up as the result of analysis of expert assessments with the help of organizational culture methods developed by the Organizational Cultural Assessment Instrument of K. Сameron and R. Quinn. Empirical data are taken from sociological research involving 384 respondents from 18 universities representing 12 regions of the Russian Federation. Results. It is shown that activity of the considered target bunches is under significant influence of hierarchical (bureaucratic) organizational culture. This objective circumstance of proceeding transformation processes forms the basis for fragmentation of existing academic identity into those intra-university bunches which are combined both in terms of valuable patterns of generations and patterns formed under the influence of social and economic conditions. Interference of various age-grade valuable patterns under permanent current transformation invokes escalation of strife, its minimum level is reached in identical age-grades of professors and lectures staff (“management academics”) and administrative managing staff (“academic managers”). A certain influence on the level of conflicts between the target groups under consideration is produced by the degree of goals adequacy and objectives of the university available resources (competence, material, technical, and financial base). Discussion and Conclusion. The novelty of the conducted research lies in consideration of conflict problems in universities arisen from the increasing differentiation of general cultural vectors of university communities. Complex, sustainable and reproducible nature of this social phenomenon, linking together both value and behavioral aspects of university communities, requires a transformation of research tactics. The research materials might be useful in practical work of heads of universities as scientific and methodological recommendations for the study and prediction of conflict processes in universities. © 2019 National Research Ogarev Mordovia State University. All rights reserved.Russian Foundation for Fundamental Investigations, RFFI18-411-130018р_а, 8.1.53.2018Funding: The authors received the support of the Russian Foundation of Fundamental Research and the Government of the Republic of Mordovia within the framework of Project 18-411-130018р_а “The organizational culture of industrial enterprises of the Republic of Mordovia (at the example of the innovative and industrial clusters)”; the article also relies on results obtained in the course of Project No. 8.1.53.2018 within the framework of the Program for Boosting Competitiveness of National Research Tomsk State University

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

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

RISCI - Repeat Induced Sequence Changes Identifier: a comprehensive, comparative genomics-based, in silico subtractive hybridization pipeline to identify repeat induced sequence changes in closely related genomes

<p>Abstract</p> <p>Background -</p> <p>The availability of multiple whole genome sequences has facilitated <it>in silico </it>identification of fixed and polymorphic transposable elements (TE). Whereas polymorphic loci serve as makers for phylogenetic and forensic analysis, fixed species-specific transposon insertions, when compared to orthologous loci in other closely related species, may give insights into their evolutionary significance. Besides, TE insertions are not isolated events and are frequently associated with subtle sequence changes concurrent with insertion or post insertion. These include duplication of target site, 3' and 5' flank transduction, deletion of the target locus, 5' truncation or partial deletion and inversion of the transposon, and post insertion changes like inter or intra element recombination, disruption etc. Although such changes have been studied independently, no automated platform to identify differential transposon insertions and the associated array of sequence changes in genomes of the same or closely related species is available till date. To this end, we have designed RISCI - 'Repeat Induced Sequence Changes Identifier' - a comprehensive, comparative genomics-based, <it>in silico </it>subtractive hybridization pipeline to identify differential transposon insertions and associated sequence changes using specific alignment signatures, which may then be examined for their downstream effects.</p> <p>Results -</p> <p>We showcase the utility of RISCI by comparing full length and truncated L1HS and AluYa5 retrotransposons in the reference human genome with the chimpanzee genome and the alternate human assemblies (Celera and HuRef). Comparison of the reference human genome with alternate human assemblies using RISCI predicts 14 novel polymorphisms in full length L1HS, 24 in truncated L1HS and 140 novel polymorphisms in AluYa5 insertions, besides several insertion and post insertion changes. We present comparison with two previous studies to show that RISCI predictions are broadly in agreement with earlier reports. We also demonstrate its versatility by comparing various strains of <it>Mycobacterium tuberculosis </it>for IS 6100 insertion polymorphism.</p> <p>Conclusions -</p> <p>RISCI combines comparative genomics with subtractive hybridization, inferring changes only when exclusive to one of the two genomes being compared. The pipeline is generic and may be applied to most transposons and to any two or more genomes sharing high sequence similarity. Such comparisons, when performed on a larger scale, may pull out a few critical events, which may have seeded the divergence between the two species under comparison.</p

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

ORGANIZATIONAL CULTURE OF RUSSIAN UNIVERSITIES: EXPECTATIONS AND REALITIES

The article analyzes changes in the profile of organizational culture of an average Russian university during the last 13 years (2003–2016), diagnosed with the use of OCAI methods. The research base of the article consists of poll results obtained by the authors in 2003–2005 and 2016. It is shown that during that period of time Russian higher education demonstrated significant deviation of university organizational culture from its planned state. Modernization processes in higher education caused universities to form adaptation reactions different from those designed at the stage of designing new development institutions. Research data allow identifying a gap between expectations concerning modernization of university organizational couture and real trends, including the growth of bureaucratic component and decrease of real autonomy and independence of academic staff, increased imbalance in corporate values of university communities creating new risks and threats for higher education development. The influence of such factors as university type, respondent’s position, profile of subjects taught on the cultural mindset of university staff was also defined. The novelty of the research is in the analysis of change dynamics in university organizational culture, defining more complicated mechanisms of its transformation and development that do not allow implementing simple linear solutions for forming modern university culture