Similarity search for local protein structures at atomic resolution by exploiting a database management system

A method to search for local structural similarities in proteins at atomic resolution is presented. It is demonstrated that a huge amount of structural data can be handled within a reasonable CPU time by using a conventional relational database management system with appropriate indexing of geometric data. This method, which we call geometric indexing, can enumerate ligand binding sites that are structurally similar to sub-structures of a query protein among more than 160,000 possible candidates within a few hours of CPU time on an ordinary desktop computer. After detecting a set of high scoring ligand binding sites by the geometric indexing search, structural alignments at atomic resolution are constructed by iteratively applying the Hungarian algorithm, and the statistical significance of the final score is estimated from an empirical model based on a gamma distribution. Applications of this method to several protein structures clearly shows that significant similarities can be detected between local structures of non-homologous as well as homologous proteins.Comment: 29 pages, 8 figures, 3 table

Effects of the Neutron Spin-Orbit Density on Nuclear Charge Density in Relativistic Models

The neutron spin-orbit density contributes to the nuclear charge density as a relativistic effect. The contribution is enhanced by the effective mass stemming from the Lorentz-scalar potential in relativistic models. This enhancement explains well the difference between the cross sections of elastic electron scattering off $^{40}$Ca and $^{48}$Ca which was not reproduced in non-relativistic models. The spin-orbit density will be examined in more detail in electron scattering off unstable nuclei which would be available in the future.Comment: 4 pages with 3 eps figures, revte

Supramolecular copolymerization driven by integrative self-sorting of hydrogen-bonded rosettes.

Molecular recognition to preorganize noncovalently polymerizable supramolecular complexes is a characteristic process of natural supramolecular polymers, and such recognition processes allow for dynamic self-alteration, yielding complex polymer systems with extraordinarily high efficiency in their targeted function. We herein show an example of such molecular recognition-controlled kinetic assembly/disassembly processes within artificial supramolecular polymer systems using six-membered hydrogen-bonded supramolecular complexes (rosettes). Electron-rich and poor monomers are prepared that kinetically coassemble through a temperature-controlled protocol into amorphous coaggregates comprising a diverse mixture of rosettes. Over days, the electrostatic interaction between two monomers induces an integrative self-sorting of rosettes. While the electron-rich monomer inherently forms toroidal homopolymers, the additional electrostatic interaction that can also guide rosette association allows helicoidal growth of supramolecular copolymers that are comprised of an alternating array of two monomers. Upon heating, the helicoidal copolymers undergo a catastrophic transition into amorphous coaggregates via entropy-driven randomization of the monomers in the rosette

Dolosigranulum pigrum modulates immunity against SARS-CoV-2 in respiratory epithelial cells

In a previous work, we demonstrated that nasally administered Dolosigranulum pigrum 040417 beneficially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 3 (TLR3) and improved protection against Respiratory Syncytial Virus (RSV) in mice. In this work, we aimed to evaluate the immunomodulatory effects of D. pigrum 040417 in human respiratory epithelial cells and the potential ability of this immunobiotic bacterium to in-crease the protection against Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The respiratory commensal bacterium D. pigrum 040417 differentially modulated the production of IFN-β, IL-6, CXCL8, CCL5 and CXCL10 in the culture supernatants of Calu-3 cells stimulated with poly(I:C) or challenged with SARS-CoV-2. The differential cytokine profile induced by the 040417 strain was associated with a significant reduction in viral replication and cellular damage after coronavirus infection. Of note, D. pigrum 030918 was not able to modify the resistance of Calu-3 cells to SARS-CoV-2 infection, indicating a strain-specific immunomodulatory effect for respiratory commensal bacteria. The findings of this work improve our understanding of the immunological mechanisms involved in the modulation of respiratory immunity induced by respiratory commensal bacteria, by demonstrating their specific effect on respiratory epithelial cells. In addition, the results suggest that particular strains such as D. pigrum 040417 could be used as a promising alternative for combating SARS-CoV-2 and reducing the severity of COVID-19.Fil: Islam, Md Aminul. Tohoku University; Japón. Bangladesh Agricultural University; BangladeshFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Melnikov, Vyacheslav. Gabrichevsky Research Institute for Epidemiology and Microbiology; RusiaFil: Andrade, Bruno G. N.. Munster Technological University; IrlandaFil: Cuadrat, Rafael R. C.. Berlín Institute for Medical Systems Biology; AlemaniaFil: Kitazawa, Haruki. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Non-uniform Photoinduced Unfolding of Supramolecular Polymers Leading to Topological Block Nanofibers

Synthesis of one-dimensional nanofibers with distinct topological (higher-order structural) domains in the same main chain is one of the challenging topics in modern supramolecular polymer chemistry. Non-uniform structural transformation of supramolecular polymer chains by external stimuli may enable preparation of such nanofibers. To demonstrate feasibility of this post-polymerization strategy, we prepared a photoresponsive helically folded supramolecular polymers from a barbiturate monomer containing an azobenzene-embedded rigid π-conjugated scaffold. In contrast to previous helically folded supramolecular polymers composed of a more flexible azobenzene monomer, UV-light induced unfolding of the newly prepared helically folded supramolecular polymers occurred nonuniformly, affording topological block copolymers consisting of folded and unfolded domains. The formation of such blocky copolymers indicates that the photoinduced unfolding of the helically folded structures initiates from relatively flexible parts such as termini or defects. Spontaneous refolding of the unfolded domains was observed after visible-light irradiation followed by aging to restore fully folded structures

Self-folding of supramolecular polymers into bioinspired topology.

Folding one-dimensional polymer chains into well-defined topologies represents an important organization process for proteins, but replicating this process for supramolecular polymers remains a challenging task. We report supramolecular polymers that can fold into protein-like topologies. Our approach is based on curvature-forming supramolecular rosettes, which affords kinetic control over the extent of helical folding in the resulting supramolecular fibers by changing the cooling rate for polymerization. When using a slow cooling rate, we obtained misfolded fibers containing a minor amount of helical domains that folded on a time scale of days into unique topologies reminiscent of the protein tertiary structures. Thermodynamic analysis of fibers with varying degrees of folding revealed that the folding is accompanied by a large enthalpic gain. The self-folding proceeds via ordering of misfolded domains in the main chain using helical domains as templates, as fully misfolded fibers prepared by a fast cooling rate do not self-fold

3D mappings by generalized joukowski transformations

The classical Joukowski transformation plays an important role in di erent applications of conformal mappings, in particular in the study of ows around the so-called Joukowski airfoils. In the 1980s H. Haruki and M. Barran studied generalized Joukowski transformations of higher order in the complex plane from the view point of functional equations. The aim of our contribution is to study the analogue of those generalized Joukowski transformations in Euclidean spaces of arbitrary higher dimension by methods of hypercomplex analysis. They reveal new insights in the use of generalized holomorphic functions as tools for quasi-conformal mappings. The computational experiences focus on 3D-mappings of order 2 and their properties and visualizations for di erent geometric con gurations, but our approach is not restricted neither with respect to the dimension nor to the order.Financial support from "Center for Research and Development in Mathematics and Applications" of the University of Aveiro, through the Portuguese Foundation for Science and Technology (FCT), is gratefully acknowledged. The research of the first author was also supported by the FCT under the fellowship SFRH/BD/44999/2008. Moreover, the authors would like to thank the anonymous referees for their helpful comments and suggestions which improved greatly the final manuscript

Comprehensive structural classification of ligand binding motifs in proteins

Comprehensive knowledge of protein-ligand interactions should provide a useful basis for annotating protein functions, studying protein evolution, engineering enzymatic activity, and designing drugs. To investigate the diversity and universality of ligand binding sites in protein structures, we conducted the all-against-all atomic-level structural comparison of over 180,000 ligand binding sites found in all the known structures in the Protein Data Bank by using a recently developed database search and alignment algorithm. By applying a hybrid top-down-bottom-up clustering analysis to the comparison results, we determined approximately 3000 well-defined structural motifs of ligand binding sites. Apart from a handful of exceptions, most structural motifs were found to be confined within single families or superfamilies, and to be associated with particular ligands. Furthermore, we analyzed the components of the similarity network and enumerated more than 4000 pairs of ligand binding sites that were shared across different protein folds.Comment: 13 pages, 8 figure

Immunobiotic lactobacilli improve resistance of respiratory epithelial cells to sars-cov-2 infection

Previously, we reported that immunomodulatory lactobacilli, nasally administered, benefi-cially regulated the lung antiviral innate immune response induced by Toll-like receptor 3 (TLR3) activation and improved protection against the respiratory pathogens, influenza virus and respiratory syncytial virus in mice. Here, we assessed the immunomodulatory effects of viable and non-viable Lactiplantibacillus plantarum strains in human respiratory epithelial cells (Calu-3 cells) and the capacity of these immunobiotic lactobacilli to reduce their susceptibility to the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immunobiotic L. plantarum MPL16 and CRL1506 differentially modulated IFN-β, IL-6, CXCL8, CCL5 and CXCL10 production and IFNAR2, DDX58, Mx1 and OAS1 expression in Calu-3 cells stimulated with the TLR3 agonist poly(I:C). Furthermore, the MPL16 and CRL1506 strains increased the resistance of Calu-3 cells to the challenge with SARS-CoV-2. L. plantarum MPL16 induced these beneficial effects more efficiently than the CRL1506 strain. Of note, neither non-viable MPL16 and CRL1506 strains nor the non-immunomodulatory strains L. plantarum CRL1905 and MPL18 could modify the resistance of Calu-3 cells to SARS-CoV-2 infection or the immune response to poly(I:C) challenge. To date, the potential beneficial effects of immunomodulatory probiotics on SARS-CoV-2 infection and COVID-19 outcome have been extrapolated from studies carried out in the context of other viral pathogens. To the best of our knowledge, this is the first demonstration of the ability of immunomodulatory lactobacilli to positively influence the replication of the new coronavirus. Further mechanistic studies and in vivo experiments in animal models of SARS-CoV-2 infection are necessary to identify specific strains of beneficial immunobiotic lactobacilli like L. plantarum MPL16 or CRL1506 for the prevention or treatment of the COVID-19.Fil: Islam, Md Aminul. Tohoku University; JapónFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Tomokiyo, Mikado. Tohoku University; JapónFil: Valdéz, Juan Carlos. Universidad Nacional de Tucumán; ArgentinaFil: Sacur, Jacinto Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Andrade, Bruno G. N.. No especifíca;Fil: Cuadrat, Rafael R. C.. No especifíca;Fil: Kitazawa, Haruki. Tohoku University; JapónFil: Villena, Julio Cesar. Tohoku University; Japón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin