Background: Seafarers are amongst occupational groups with the highest risk for stress, a factor known to impact on mental health. Psychological issues such as depression, anxiety, suicide, and alcohol or drug dependence are recognized health problems within the maritime sector. The primary aim of this study was to identify which individual and occupational factors, known to impact on psychological functioning across the maritime industry and other sectors, best predict perceived stress and job satisfaction among a sample of merchant seafarers. Methods: Secondary data analysis was conducted using a work experiences and attitudes questionnaire administered by a large shipping company to seafarers within their organization. Structural equation modeling was conducted using a proposed theoretical model of perceived stress and job satisfaction in a sample of merchant seafarers. Results: While the structural equation model produced acceptable fit to the sample data according to numerous goodness-of-fit statistics, the comparative fit index and Tucker-Lewis index results indicated less than satisfactory model fit. The model explained 23.8% of variance in the criterion variable of perceived stress, and the strongest predictive effect was for dispositional resilience. The model explained 70.6% of variance in the criterion variable of job satisfaction, and the strongest predictive effect was for instrumental work support. Conclusion: When addressing the psychosocial well-being of merchant seafarers, findings of this study suggest that dispositional resilience may be a particularly important factor with regards to perceived stress, while instrumental work support appears to be a critical factor in relation to job satisfaction. Importantly, however, an overall work environment that is perceived by employees as supportive, equal and just is a cornerstone for the psychosocial well-being of seafarers.

• Klíčová slova
• job satisfaction, maritime, merchant seafarers, perceived stress, psychosocial well-being, structural equation modeling,
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: T-cell receptor (TCR) recognition of foreign peptides presented by the major histocompatibility complex (MHC) initiates the adaptive immune response against pathogens. While a large number of TCR sequences specific to different antigenic peptides are known to date, the structural data describing the conformation and contacting residues for TCR-peptide-MHC complexes is relatively limited. In the present study we aim to extend and analyze the set of available structures by performing highly accurate template-based modeling of these complexes using TCR sequences with known specificity. METHODS: Identification of CDR3 sequences and their further clustering, based on available spatial structures, V- and J-genes of corresponding T-cell receptors, and epitopes, was performed using the VDJdb database. Modeling of the selected CDR3 loops was conducted using a stepwise introduction of single amino acid substitutions to the template PDB structures, followed by optimization of the TCR-peptide-MHC contacting interface using the Rosetta package applications. Statistical analysis and recursive feature elimination procedures were carried out on computed energy values and properties of contacting amino acid residues between CDR3 loops and peptides, using R. RESULTS: Using the set of 29 complex templates (including a template with SARS-CoV-2 antigen) and 732 specificity records, we built a database of 1585 model structures carrying substitutions in either TCRα or TCRβ chains with some models representing the result of different mutation pathways for the same final structure. This database allowed us to analyze features of amino acid contacts in TCR - peptide interfaces that govern antigen recognition preferences and interpret these interactions in terms of physicochemical properties of interacting residues. CONCLUSION: Our results provide a methodology for creating high-quality TCR-peptide-MHC models for antigens of interest that can be utilized to predict TCR specificity.

• Klíčová slova
• T-cell receptor, TCR-peptide-MHC complex, antigen recognition, database, structural modeling,
• MeSH
• aminokyseliny MeSH
• antigenní specifita receptorů T-buněk MeSH
• COVID-19 * MeSH
• komplement MeSH
• lidé MeSH
• SARS-CoV-2 MeSH
• specificita protilátek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• komplement MeSH

Beside of the protein crystallography or NMR, another attractive option in protein structure analysis has recently appeared: computer modeling of the protein structure based on homology and similarity with proteins of already known structures. We have used the combination of computer modeling with spectroscopic techniques, such as steady-state or time-resolved fluorescence spectroscopy, and with molecular biology techniques. This method could provide useful structural information in the cases where crystal or NMR structure is not available. Molecular modeling of the ATP site within the H4-H5-loop revealed eight amino acids residues, namely besides the previously reported amino acids Asp443, Lys480, Lys501, Gly502 and Arg544, also Glu446, Phe475 and Gln482, which form the complete ATP recognition site. Moreover, we have proved that a hydrogen bond between Arg423 and Glu472 supports the connection of two opposite halves of the ATP-binding pocket. Similarly, the conserved residue Pro489 is important for the proper interaction of the third and fourth beta-strands, which both contain residues that take part in the ATP-binding. Alternatively, molecular dynamics simulation combined with dynamic fluorescence spectroscopy revealed that 14-3-3 zeta C-terminal stretch is directly involved in the interaction of 14-3-3 protein with the ligand. Phosphorylation at Thr232 induces a conformational change of the C-terminus, which is presumably responsible for observed inhibition of binding abilities. Phosphorylation at Thr232 induces more extended conformation of 14-3-3zeta C-terminal stretch and changes its interaction with the rest of the 14-3-3 molecule. This could explain negative regulatory effect of phosphorylation at Thr232 on 14-3-3 binding properties.

• MeSH
• adenosintrifosfát chemie   metabolismus   MeSH
• alkoholoxidoreduktasy MeSH
• DNA vazebné proteiny fyziologie   MeSH
• fluorescenční spektrometrie metody   MeSH
• fosfoproteiny fyziologie   MeSH
• fosforylace MeSH
• konformace proteinů * MeSH
• konzervovaná sekvence MeSH
• molekulární modely * MeSH
• počítačová simulace * MeSH
• proteiny 14-3-3 chemie   metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• sodíko-draslíková ATPasa chemie   fyziologie   MeSH
• threonin fyziologie   MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosintrifosfát MeSH
• alkoholoxidoreduktasy MeSH
• C-terminal binding protein MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• fosfoproteiny MeSH
• proteiny 14-3-3 MeSH
• sodíko-draslíková ATPasa MeSH
• threonin MeSH

NKR-P1C is an activating immune receptor expressed on the surface of mouse natural killer cells. It has been widely used as a marker for NK cell identification in different mice strains. Recently we solved a crystal structure of the C-type lectin-like domain of a homologous protein, NKR-P1A, using X-ray crystallography and also described the strategy for rapid characterization of the protein conformation in solution. This procedure utilized chemical cross-linking, hydrogen/deuterium exchange, and molecular modeling. It was found that the solution structure differs from the crystal structure in the conformation of the loop region. The loop, detached from the protein compact core in the crystal structure, is closely attached to the core of the protein in solution. Here we present and interpret the solution structure of the C-type lectin-like domain of NKR-P1C using chemical cross-linking and molecular modeling. The validation of the model and conformation of the loop region in NKR-P1C were addressed using ion-mobility mass spectrometry.

• MeSH
• antigeny Ly chemie   metabolismus   MeSH
• hmotnostní spektrometrie metody   MeSH
• krystalografie rentgenová metody   MeSH
• lektinové receptory NK-buněk - podrodina B chemie   metabolismus   MeSH
• lidé MeSH
• lymfocyty metabolismus   MeSH
• molekulární modely * MeSH
• molekulární sekvence - údaje MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• sekundární struktura proteinů MeSH
• sekvence aminokyselin MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny Ly MeSH
• Klrb1c protein, mouse MeSH Prohlížeč
• lektinové receptory NK-buněk - podrodina B MeSH

Homology modeling is a method for building protein 3D structures using protein primary sequence and utilizing prior knowledge gained from structural similarities with other proteins. The homology modeling process is done in sequential steps where sequence/structure alignment is optimized, then a backbone is built and later, side-chains are added. Once the low-homology loops are modeled, the whole 3D structure is optimized and validated. In the past three decades, a few collective and collaborative initiatives allowed for continuous progress in both homology and ab initio modeling. Critical Assessment of protein Structure Prediction (CASP) is a worldwide community experiment that has historically recorded the progress in this field. Folding@Home and Rosetta@Home are examples of crowd-sourcing initiatives where the community is sharing computational resources, whereas RosettaCommons is an example of an initiative where a community is sharing a codebase for the development of computational algorithms. Foldit is another initiative where participants compete with each other in a protein folding video game to predict 3D structure. In the past few years, contact maps deep machine learning was introduced to the 3D structure prediction process, adding more information and increasing the accuracy of models significantly. In this review, we will take the reader in a journey of exploration from the beginnings to the most recent turnabouts, which have revolutionized the field of homology modeling. Moreover, we discuss the new trends emerging in this rapidly growing field.

• Klíčová slova
• Artificial intelligence, Collective intelligence, Homology modeling, Machine learning, Protein 3D structure, Structural bioinformatics,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The ordering of three different sizes of quaternary ammonium salts (QUATs) has been studied with respect to concentration of guests in the host's interlayer gallery. From the modeling, we could verify that small molecules of n-butylammonium salt build a monolayer structure in the vermiculite gallery without reference to concentration. On the other hand, the larger molecules of dodecyltrimethylammonium and dioctadecyldimethylammonium salts are responsive to the numbers of their molecules in the interlayer space of the host, building mono- or bilayered structures. Supersaturated structure of both QUATs keep an arrangement of alkyl chains nearly perpendicular to silicate layers, while only saturated samples exhibit tilted alkyl chains in the gallery. The ordering changes bring out the calculation of mean crystallite size. Low values of the nonbond energy of supersaturated forms predict that those organovermiculites will readily exfoliate, e.g., in polymer/clay nanocomposite.

• Publikační typ
• časopisecké články MeSH

The purpose of this quick guide is to help new modelers who have little or no background in comparative modeling yet are keen to produce high-resolution protein 3D structures for their study by following systematic good modeling practices, using affordable personal computers or online computational resources. Through the available experimental 3D-structure repositories, the modeler should be able to access and use the atomic coordinates for building homology models. We also aim to provide the modeler with a rationale behind making a simple list of atomic coordinates suitable for computational analysis abiding to principles of physics (e.g., molecular mechanics). Keeping that objective in mind, these quick tips cover the process of homology modeling and some postmodeling computations such as molecular docking and molecular dynamics (MD). A brief section was left for modeling nonprotein molecules, and a short case study of homology modeling is discussed.

• MeSH
• algoritmy MeSH
• aminokyseliny chemie   MeSH
• biologické modely MeSH
• databáze proteinů MeSH
• internet MeSH
• ionty MeSH
• koncentrace vodíkových iontů MeSH
• ligandy MeSH
• počítačová simulace MeSH
• posttranslační úpravy proteinů MeSH
• proteiny chemie   MeSH
• rozpouštědla MeSH
• sbalování proteinů MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• software MeSH
• strojové učení MeSH
• strukturní homologie proteinů MeSH
• voda MeSH
• výpočetní biologie metody   MeSH
• zobrazování trojrozměrné metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• ionty MeSH
• ligandy MeSH
• proteiny MeSH
• rozpouštědla MeSH
• voda MeSH

A strategy for the structure analysis of intercalated layer silicates based on a combination of modeling (i.e. force field calculations) and experiment is presented. Modeling in conjunction with experiment enables us to analyze the disordered intercalated structures of layer silicates where conventional diffraction analysis fails. Experiment plays a key role in the modeling strategy and in corroboration of the modeling results. X-ray powder diffraction and IR spectroscopy were found to be very useful complementary experiments to molecular modeling. Molecular mechanics and molecular dynamics simulations were carried out in the Cerius2 and Materials Studio modeling environments. An overview is given of the structures of layer silicates, especially smectites intercalated with various inorganic and organic guest species. Special attention is paid to the ordering of guests in the interlayer space, as it is important for the practical applications of these intercalates, where the interlayer porosity, photofunctions, etc. must be controlled. Figure Structure of montmorillonite intercalated with octadecylamine via ion-dipole interaction with the maximum concentration of guests corresponding to the monolayer arrangement of guests with basal spacing 33.3 A. The Na cations remaining in the interlayer are visualized as pink balls

• MeSH
• difrakce rentgenového záření MeSH
• molekulární modely * MeSH
• molekulární struktura MeSH
• rhodaminy chemie   MeSH
• silikáty chemie   MeSH
• spektrofotometrie infračervená MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• rhodamine B MeSH Prohlížeč
• rhodaminy MeSH
• silikáty MeSH

The ankyrin transient receptor potential channel TRPA1 is a polymodal sensor for noxious stimuli, and hence a promising target for treating chronic pain. This tetrameric six-transmembrane segment (S1-S6) channel can be activated by various pungent chemicals, such as allyl isothiocyanate or cinnamaldehyde, but also by intracellular Ca(2+) or depolarizing voltages. Within the S4-S5 linker of human TRPA1, a gain-of-function mutation, N855S, was recently found to underlie familial episodic pain syndrome, manifested by bouts of severe upper body pain, triggered by physical stress, fasting, or cold. To clarify the structural basis for this channelopathy, we derive a structural model of TRPA1 by combining homology modeling, molecular dynamics simulations, point mutagenesis and electrophysiology. In the vicinity of N855, the model reveals inter-subunit salt bridges between E854 and K868. Using the heterologous expression of recombinant wild-type and mutant TRPA1 channels in HEK293T cells, we indeed found that the charge-reversal mutants E854R and K868E exhibited dramatically reduced responses to chemical and voltage stimuli, whereas the charge-swapping mutation E854R/K868E substantially rescued their functionalities. Moreover, mutation analysis of highly conserved charged residues within the S4-S5 region revealed a gain-of-function phenotype for R852E with an increased basal channel activity, a loss of Ca(2+)-induced potentiation and an accelerated Ca(2+)-dependent inactivation. Based on the model and on a comparison with the recently revealed atomic-level structure of the related channel TRPV1, we propose that inter-subunit salt bridges between adjacent S4-S5 regions are crucial for stabilizing the conformations associated with chemically and voltage-induced gating of the TRPA1 ion channel.

• Klíčová slova
• Ankyrin receptor subtype 1, Homology modeling, Molecular dynamics, Mutagenesis, S4–S5-linker, Transient receptor potential,
• MeSH
• asparagin genetika   MeSH
• elektrická stimulace MeSH
• gating iontového kanálu účinky léků   fyziologie   MeSH
• HEK293 buňky MeSH
• isothiokyanatany farmakologie   MeSH
• kationtové kanály TRP chemie   genetika   metabolismus   MeSH
• kationtový kanál TRPA1 MeSH
• lidé MeSH
• membránové potenciály genetika   MeSH
• metoda terčíkového zámku MeSH
• molekulární modely * MeSH
• mutace genetika   MeSH
• mutageneze MeSH
• proteiny nervové tkáně chemie   genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• serin genetika   MeSH
• terciární struktura proteinů MeSH
• transfekce MeSH
• vápník metabolismus   MeSH
• vápníkové kanály chemie   genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate MeSH Prohlížeč
• asparagin MeSH
• isothiokyanatany MeSH
• kationtové kanály TRP MeSH
• kationtový kanál TRPA1 MeSH
• proteiny nervové tkáně MeSH
• serin MeSH
• TRPA1 protein, human MeSH Prohlížeč
• vápník MeSH
• vápníkové kanály MeSH

The objective of the studies was to synthesize and characterize new mono- and diesters with an imidazoquinolin-2-one ring with the use of 2,3-dihydro-2-thioxo-1H-imidazo[4 ,5-c]-quinolin-4(5H)-ones and ethyl bromoacetate. The products were isolated at high yield and characterized by instrumental methods (IR, 1H-, 13C-, and 15N- NMR, MS-ESI, HR-MS, EA). In order to clarify the places of substitution and the structure of the derivatives obtained, molecular modeling of substrates and products was performed. Consideration of the possible tautomeric structures of the substrates confirmed the existence only the most stable keto form. Based on the free energy of monosubstituted ester derivatives, the most stable form were derivatives substituted at sulfur atom of enolic form the used imidazoquinolones. Enolic form referred only to nitrogen atom no 1. The modeling results were consistent with the experimental data. The HOMO electron densities at selected atoms of each substrate has shown that the most reactive atom is sulfur atom. It explained the formation of monoderivatives substituted at sulfur atom. The diester derivatives of the used imidazoquinolones had second substituent at nitrogen atom no. 3. The new diesters can be used as raw material for synthesis of thermally stable polymers, and they can also have biological activity.

• Klíčová slova
• 3-hydroxyquinolinediones, ammonium thiocyanate, debenzylation, molecular modeling, thioxoimidazoquinolinone ring,
• MeSH
• chinolony chemická syntéza   chemie   MeSH
• estery chemie   MeSH
• imidazoly chemie   MeSH
• kvantová teorie MeSH
• molekulární konformace MeSH
• molekulární modely * MeSH
• thiokyanatany chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chinolony MeSH
• estery MeSH
• imidazole MeSH Prohlížeč
• imidazoly MeSH
• thiocyanic acid MeSH Prohlížeč
• thiokyanatany MeSH