cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.825491.v1
title: Insights on pH-dependent conformational changes of mosquito odorant binding proteins by molecular dynamics simulations

description: Chemical recognition plays an important role for the survival and reproduction of many insect species. Odorant binding proteins (OBPs) are the primary components of the insect olfactory mechanism and have been documented to play an important role in the host-seeking mechanism of mosquitoes. They are “transport proteins” believed to transport odorant molecules from the external environment to their respective membrane targets, the olfactory receptors. The mechanism by which this transport occurs in mosquitoes remains a conundrum in this field. Nevertheless, OBPs have proved to be amenable to conformational changes mediated by a pH change in other insect species. In this paper, the effect of pH on the conformational flexibility of mosquito OBPs is assessed computationally using molecular dynamics simulations of a mosquito OBP “CquiOBP1” bound to its pheromone 3OG (PDB ID: 3OGN). Conformational twist of a loop, driven by a set of well-characterized changes in intramolecular interactions of the loop, is demonstrated. The concomitant (i) closure of what is believed to be the entrance of the binding pocket, (ii) expansion of what could be an exit site, and (iii) migration of the ligand towards this putative exit site provide preliminary insights into the mechanism of ligand binding and release of these proteins in mosquitoes. The correlation of our results with previous experimental observations based on NMR studies help us provide a cardinal illustration on one of the probable dynamics and mechanism by which certain mosquito OBPs could deliver their ligand to their membrane-bound receptors at specific pH conditions.
DOI: 10.6084/m9.figshare.825485
title: Structure-based design and experimental engineering of a plant virus nanoparticle for the presentation of immunogenic epitopes and as a drug carrier

description: Biomaterials research for the discovery of new generation nanoparticles is one of the most active areas of nanotechnoloy. In the search of nature-made nanometer-sized objects, plant virus particles appear as symmetrically defined entities that can be formed by protein self-assembly. In particular, in the field of plant virology, there is plenty of literature available describing the exploitation of plant viral cages to produce safe vaccine vehicles and nanoparticles for drug delivery. In this context, we have investigated on the use of the artichoke mottled crinkle virus (AMCV) capsid both as a carrier of immunogenic epitopes and for the delivery of anticancer molecules. A dual approach that combines both <i>in silico</i> tools and experimental virology was applied for the rational design of immunologically active chimeric virus-like particles (VLPs) carrying immunogenic peptides. The atomic structures of wild type (wt) and chimeric VLPs were obtained by homology modeling. The effects of insertion of the HIV-1 2F5 neutralizing epitope on the structural stability of chimeric VLPs were predicted and assessed by detailed inspection of the nanoparticle intersubunit interactions at atomic level. Wt and chimeric VLPs, exposing on their surface the 2F5 epitope, were successfully produced in plants. In addition, we demonstrated that AMCV capsids could also function as drug delivery vehicles able to load the chemotherapeutic drug doxorubicin. To our knowledge, this is the first systematic predictive and empirical research addressing the question of how this icosahedral virus can be used for the production of both VLPs and viral nanoparticles for biomedical applications.
DOI: 10.6084/m9.figshare.825485.v2
title: Structure-based design and experimental engineering of a plant virus nanoparticle for the presentation of immunogenic epitopes and as a drug carrier

description: Biomaterials research for the discovery of new generation nanoparticles is one of the most active areas of nanotechnoloy. In the search of nature-made nanometer-sized objects, plant virus particles appear as symmetrically defined entities that can be formed by protein self-assembly. In particular, in the field of plant virology, there is plenty of literature available describing the exploitation of plant viral cages to produce safe vaccine vehicles and nanoparticles for drug delivery. In this context, we have investigated on the use of the artichoke mottled crinkle virus (AMCV) capsid both as a carrier of immunogenic epitopes and for the delivery of anticancer molecules. A dual approach that combines both <i>in silico</i> tools and experimental virology was applied for the rational design of immunologically active chimeric virus-like particles (VLPs) carrying immunogenic peptides. The atomic structures of wild type (wt) and chimeric VLPs were obtained by homology modeling. The effects of insertion of the HIV-1 2F5 neutralizing epitope on the structural stability of chimeric VLPs were predicted and assessed by detailed inspection of the nanoparticle intersubunit interactions at atomic level. Wt and chimeric VLPs, exposing on their surface the 2F5 epitope, were successfully produced in plants. In addition, we demonstrated that AMCV capsids could also function as drug delivery vehicles able to load the chemotherapeutic drug doxorubicin. To our knowledge, this is the first systematic predictive and empirical research addressing the question of how this icosahedral virus can be used for the production of both VLPs and viral nanoparticles for biomedical applications.
DOI: 10.6084/m9.figshare.825485.v1
title: Structure-based design and experimental engineering of a plant virus nanoparticle for the presentation of immunogenic epitopes and as a drug carrier

description: Biomaterials research for the discovery of new generation nanoparticles is one of the most active areas of nanotechnoloy. In the search of nature-made nanometer-sized objects, plant virus particles appear as symmetrically defined entities that can be formed by protein self-assembly. In particular, in the field of plant virology, there is plenty of literature available describing the exploitation of plant viral cages to produce safe vaccine vehicles and nanoparticles for drug delivery. In this context, we have investigated on the use of the artichoke mottled crinkle virus (AMCV) capsid both as a carrier of immunogenic epitopes and for the delivery of anticancer molecules. A dual approach that combines both <i>in silico</i> tools and experimental virology was applied for the rational design of immunologically active chimeric virus-like particles (VLPs) carrying immunogenic peptides. The atomic structures of wild type (wt) and chimeric VLPs were obtained by homology modeling. The effects of insertion of the HIV-1 2F5 neutralizing epitope on the structural stability of chimeric VLPs were predicted and assessed by detailed inspection of the nanoparticle intersubunit interactions at atomic level. Wt and chimeric VLPs, exposing on their surface the 2F5 epitope, were successfully produced in plants. In addition, we demonstrated that AMCV capsids could also function as drug delivery vehicles able to load the chemotherapeutic drug doxorubicin. To our knowledge, this is the first systematic predictive and empirical research addressing the question of how this icosahedral virus can be used for the production of both VLPs and viral nanoparticles for biomedical applications.
DOI: 10.6084/m9.figshare.825482
title: The substitutions G245C and G245D in the Zn<sup>2+</sup>-binding pocket of the p53 protein result in differences of conformational flexibility of the DNA-binding domain

description: Transcription activation of the proapoptotic target genes is a means by which the p53 protein implements its function of tumor suppression. Zn<sup>2+</sup> is a known regulator of p53 binding to the target genes. We have previously obtained an evidence that amino acid substitutions in the p53 Zn<sup>2+</sup>-binding pocket can presumably exert an influence on Zn<sup>2+</sup> position in the Zn<sup>2+</sup>-p53 complex and thereby affect p53 binding to DNA. With these background considerations, our aim was to estimate the effect of the putative changes in the Zn<sup>2+</sup> position in its binding pocket due to the G245C and G245D substitutions on the conformation of the p53 DNA-binding motif. Statistical analysis of the molecular dynamics (MD) trajectories of the mutant p53-Zn<sup>2+</sup> complexes was used to detect significant deviations in conformation of the mutant p53 forms. MD simulations demonstrated that (1) the two substitutions in the Zn<sup>2+</sup>-binding pocket caused changes in the conformation of the p53 DNA-binding motif, as compared with the wild-type (WT) p53; (2) binding of Zn<sup>2+</sup> to the p53 mutant forms reduced the effect of the substitutions on conformational change; and (3) Zn<sup>2+</sup> binding in the normal position compensated the effect of the mutations on the conformation in comparison to the altered Zn<sup>2+</sup> position.
DOI: 10.6084/m9.figshare.825481
title: Identification of self-consistent modulons from bacterial microarray expression data with the help of structured regulon gene sets

description: Identification of bacterial modulons from series of gene expression measurements on microarrays is a principal problem, especially relevant for inadequately studied but practically important species. Usage of a priori information on regulatory interactions helps to evaluate parameters for regulatory subnetwork inference. We suggest a procedure for modulon construction where a seed regulon is iteratively updated with genes having expression patterns similar to those for regulon member genes. A set of genes essential for a regulon is used to control modulon updating. Essential genes for a regulon were selected as a subset of regulon genes highly related by different measures to each other. Using <i>Escherichia coli</i> as a model, we studied how modulon identification depends on the data, including the microarray experiments set, the adopted relevance measure and the regulon itself. We have found that results of modulon identification are highly dependent on all parameters studied and thus the resulting modulon varies substantially depending on the identification procedure. Yet, modulons that were identified correctly displayed higher stability during iterations, which allows developing a procedure for reliable modulon identification in the case of less studied species where the known regulatory interactions are sparse.
DOI: 10.6084/m9.figshare.825480
title: Computational screening for new inhibitors of <i>M. tuberculosis</i> mycolyltransferases antigen 85 group of proteins as potential drug targets

description: The group of antigen 85 proteins of <i>Mycobacterium tuberculosis</i> is responsible for converting trehalose monomycolate to trehalose dimycolate, which contributes to cell wall stability. Here, we have used a serial enrichment approach to identify new potential inhibitors by searching the libraries of compounds using both 2D atom pair descriptors and binary fingerprints followed by molecular docking. Three different docking softwares AutoDock, GOLD, and LigandFit were used for docking calculations. In addition, we applied the criteria of selecting compounds with binding efficiency close to the starting known inhibitor and showing potential to form hydrogen bonds with the active site amino acid residues. The starting inhibitor was ethyl-3-phenoxybenzyl-butylphosphonate, which had IC<sub>50</sub> value of 2.0 μM in mycolyltransferase inhibition assay. Our search from more than 34 million compounds from public libraries yielded 49 compounds. Subsequently, selection was restricted to compounds conforming to the Lipinski rule of five and exhibiting hydrogen bonding to any of the amino acid residues in the active site pocket of all three proteins of antigen 85A, 85B, and 85C. Finally, we selected those ligands which were ranked top in the table with other known decoys in all the docking results. The compound NIH415032 from tuberculosis antimicrobial acquisition and coordinating facility was further examined using molecular dynamics simulations for 10 ns. These results showed that the binding is stable, although some of the hydrogen bond atom pairs varied through the course of simulation. The NIH415032 has antitubercular properties with IC<sub>90</sub> at 20 μg/ml (53.023 μM). These results will be helpful to the medicinal chemists for developing new antitubercular molecules for testing.
DOI: 10.6084/m9.figshare.825477
title: Agent-based simulation for a dual-diffusion process of influenza and human preventive behavior

description: Influenza disease diffuses from one individual to another through their close contacts, while preventive behavior propagates through inter-personal influences. These two diffusion processes take place simultaneously and interact with one another in opposite directions. Many current influenza studies consider the diffusion of influenza, but few of them have incorporated the diffusion of human preventive behavior. This article proposes an original dual-diffusion model to couple these two diffusion processes. The conceptual framework of the model incorporates these two opposite processes into a human contact network. An agent-based approach, network theory, disease model, and behavioral model are integrated to formulate the conceptual framework. Model implementation simulates an influenza epidemic in an urbanized area of one million individuals. The simulation results suggest that the proposed model offers a close representation of the observed data. The research findings will provide a more rational basis for influenza control.
DOI: 10.6084/m9.figshare.825477.v1
title: Agent-based simulation for a dual-diffusion process of influenza and human preventive behavior

description: Influenza disease diffuses from one individual to another through their close contacts, while preventive behavior propagates through inter-personal influences. These two diffusion processes take place simultaneously and interact with one another in opposite directions. Many current influenza studies consider the diffusion of influenza, but few of them have incorporated the diffusion of human preventive behavior. This article proposes an original dual-diffusion model to couple these two diffusion processes. The conceptual framework of the model incorporates these two opposite processes into a human contact network. An agent-based approach, network theory, disease model, and behavioral model are integrated to formulate the conceptual framework. Model implementation simulates an influenza epidemic in an urbanized area of one million individuals. The simulation results suggest that the proposed model offers a close representation of the observed data. The research findings will provide a more rational basis for influenza control.
DOI: 10.6084/m9.figshare.825481.v1
title: Identification of self-consistent modulons from bacterial microarray expression data with the help of structured regulon gene sets

description: Identification of bacterial modulons from series of gene expression measurements on microarrays is a principal problem, especially relevant for inadequately studied but practically important species. Usage of a priori information on regulatory interactions helps to evaluate parameters for regulatory subnetwork inference. We suggest a procedure for modulon construction where a seed regulon is iteratively updated with genes having expression patterns similar to those for regulon member genes. A set of genes essential for a regulon is used to control modulon updating. Essential genes for a regulon were selected as a subset of regulon genes highly related by different measures to each other. Using <i>Escherichia coli</i> as a model, we studied how modulon identification depends on the data, including the microarray experiments set, the adopted relevance measure and the regulon itself. We have found that results of modulon identification are highly dependent on all parameters studied and thus the resulting modulon varies substantially depending on the identification procedure. Yet, modulons that were identified correctly displayed higher stability during iterations, which allows developing a procedure for reliable modulon identification in the case of less studied species where the known regulatory interactions are sparse.
DOI: 10.6084/m9.figshare.825474
title: Network models reveal stability and structural rearrangement of signal recognition particle

description: The signal recognition particle (SRP) and its receptors (SR) mediate the cotranslational targeting of the membrane and secretory proteins in all cells. In <i>Escherichia coli</i>, SRP is composed of the Ffh protein and the 4.5S SRP RNA. Ffh is a multidomain protein comprising a methionine-rich (M) domain, a helical N domain, and a Ras-like guanine triphosphatase (GTPase) (G) domain. The N and G domains are commonly referred to as one structural unit, the NG domain. In this article, the complex structure of SRP and SR is investigated with the Gaussian network model (GNM) and anisotropic network model (ANM). GNM provides the information of structure stability. It is found that the intermolecular interactions between SRP and SR can obviously decrease the fluctuation of NG domains. Nevertheless, the large structural rearrangement will take place during the cotranslational protein targeting cycle. Hence, the moving directions of fluctuation regions are further ascertained by using cross-correlation analysis and the ANM. The NG domain of Ffh undergoes a clockwise rotation around the GM linker and the M domain of Ffh shows an opposite direction to the NG domain. These functional movements will facilitate the SRP structure to transform into the free form and the sequence-bound form. These simple coarse-grained analyses can be used as a general and quick method for the mechanism studies of protein assembly and supramolecular systems.
DOI: 10.6084/m9.figshare.825475
title: Orderly order in protein intrinsic disorder distribution: disorder in 3500 proteomes from viruses and the three domains of life

description: Intrinsically disordered proteins and intrinsically disordered protein regions are highly abundant in nature. However, the quantitative and qualitative measures of protein intrinsic disorder in species with known genomes are still not available. Furthermore, although the correlation between high fraction of disordered residues and advanced species has been reported, the details of this correlation and the connection between the disorder content and proteome complexity have not been reported as of yet. To fill this gap, we analysed entire proteomes of 3484 species from three domains of life (archaea, bacteria and eukaryotes) and from viruses. Our analysis revealed that the evolution process is characterized by distinctive patterns of changes in the protein intrinsic disorder content. We are showing here that viruses are characterized by the widest spread of the proteome disorder content (the percentage of disordered residues ranges from 7.3% in human coronavirus NL63 to 77.3% in <i>Avian carcinoma virus</i>). For several organisms, a clear correlation is seen between their disorder contents and habitats. In multicellular eukaryotes, there is a weak correlation between the complexity of an organism (evaluated as a number of different cell types) and its overall disorder content. For both the prokaryotes and eukaryotes, the disorder content is generally independent of the proteome size. However, disorder shows a sharp increase associated with the transition from prokaryotic to eukaryotic cells. This suggests that the increased disorder content in eukaryotic proteomes might be used by nature to deal with the increased cell complexity due to the appearance of the various cellular compartments.
DOI: 10.6084/m9.figshare.825480.v1
title: Computational screening for new inhibitors of <i>M. tuberculosis</i> mycolyltransferases antigen 85 group of proteins as potential drug targets

description: The group of antigen 85 proteins of <i>Mycobacterium tuberculosis</i> is responsible for converting trehalose monomycolate to trehalose dimycolate, which contributes to cell wall stability. Here, we have used a serial enrichment approach to identify new potential inhibitors by searching the libraries of compounds using both 2D atom pair descriptors and binary fingerprints followed by molecular docking. Three different docking softwares AutoDock, GOLD, and LigandFit were used for docking calculations. In addition, we applied the criteria of selecting compounds with binding efficiency close to the starting known inhibitor and showing potential to form hydrogen bonds with the active site amino acid residues. The starting inhibitor was ethyl-3-phenoxybenzyl-butylphosphonate, which had IC<sub>50</sub> value of 2.0 μM in mycolyltransferase inhibition assay. Our search from more than 34 million compounds from public libraries yielded 49 compounds. Subsequently, selection was restricted to compounds conforming to the Lipinski rule of five and exhibiting hydrogen bonding to any of the amino acid residues in the active site pocket of all three proteins of antigen 85A, 85B, and 85C. Finally, we selected those ligands which were ranked top in the table with other known decoys in all the docking results. The compound NIH415032 from tuberculosis antimicrobial acquisition and coordinating facility was further examined using molecular dynamics simulations for 10 ns. These results showed that the binding is stable, although some of the hydrogen bond atom pairs varied through the course of simulation. The NIH415032 has antitubercular properties with IC<sub>90</sub> at 20 μg/ml (53.023 μM). These results will be helpful to the medicinal chemists for developing new antitubercular molecules for testing.
DOI: 10.6084/m9.figshare.825472
title: Feeding habits and selectivity of the wide-eyed flounder, <i>Bothus podas</i> (Delaroche, 1809) (Bothidae) from the southern Tyrrhenian sea

description: In order to assess the diet composition of the wide-eyed flounder <i>Bothus podas</i>, we analysed the stomach contents of 388 specimens collected seasonally on sandy bottoms of the north-western coast of Sicily (central Mediterranean). The benthic communities in the same area were also studied in order to investigate the feeding selectivity of <i>B. podas</i>. The prey items found in the stomach contents analysed were mostly benthic organisms. The diet composition of <i>B. podas</i> was dominated by Gammaridea, Apseudidae and Cumacea that were also the most abundant categories in the benthic community. Active prey, such as benthic and epibenthic crustaceans, were highly selected, whereas molluscs and polychaetes were only occasionally ingested. Significant differences found in prey abundance by site were related to the different benthic compositions in the sites examined rather than to changes in the feeding behaviour of <i>B. podas</i>. Significant differences in diet by seasons were explained by the highest abundance of Caprellidea, Gammaridea and Cumacea in spring and summer. The observed feeding patterns were related to spatial and temporal variation of prey abundance in the benthos. As a result, <i>B. podas</i> can be considered an active opportunistic predator.