Structuprint: a scalable and extensible tool for two-dimensional representation of protein surfaces

© 2016 Kontopoulos et al.Background: The term molecular cartography encompasses a family of computational methods for two-dimensional transformation of protein structures and analysis of their physicochemical properties. The underlying algorithms comprise multiple manual steps, whereas the few existing implementations typically restrict the user to a very limited set of molecular descriptors. Results: We present Structuprint, a free standalone software that fully automates the rendering of protein surface maps, given - at the very least - a directory with a PDB file and an amino acid property. The tool comes with a default database of 328 descriptors, which can be extended or substituted by user-provided ones. The core algorithm comprises the generation of a mould of the protein surface, which is subsequently converted to a sphere and mapped to two dimensions, using the Miller cylindrical projection. Structuprint is partly optimized for multicore computers, making the rendering of animations of entire molecular dynamics simulations feasible. Conclusions: Structuprint is an efficient application, implementing a molecular cartography algorithm for protein surfaces. According to the results of a benchmark, its memory requirements and execution time are reasonable, allowing it to run even on low-end personal computers. We believe that it will be of use - primarily but not exclusively - to structural biologists and computational biochemists

Space constrained homology modelling: The paradigm of the RNA-dependent RNA polymerase of dengue (Type II) virus

Protein structure is more conserved than sequence in nature. In this direction we developed a novel methodology that significantly improves conventional homology modelling when sequence identity is low, by taking into consideration 3D structural features of the template, such as size and shape. Herein, our new homology modelling approach was applied to the homology modelling of the RNA-dependent RNA polymerase (RdRp) of dengue (type II) virus. The RdRp of dengue was chosen due to the low sequence similarity shared between the dengue virus polymerase and the available templates, while purposely avoiding to use the actual X-ray structure that is available for the dengue RdRp. The novel approach takes advantage of 3D space corresponding to protein shape and size by creating a 3D scaffold of the template structure. The dengue polymerase model built by the novel approach exhibited all features of RNA-dependent RNA polymerases and was almost identical to the X-ray structure of the dengue RdRp, as opposed to the model built by conventional homology modelling. Therefore, we propose that the space-aided homology modelling approach can be of a more general use to homology modelling of enzymes sharing low sequence similarity with the template structures. © 2013 Dimitrios Vlachakis et al

Adult Kawasaki disease in a European patient: a case report and review of the literature

© 2015 Kontopoulou et al.; licensee BioMed Central.Introduction: Kawasaki disease is an acute necrotising vasculitis of the medium- and small-sized vessels, occurring mainly in Japanese and Korean babies and children, aged 6 months to 5 years. Its main complication is damage of coronary arteries, which has the potential to be fatal. Here we report a rare case of Kawasaki disease that occurred in a 20-year-old Greek adult. Case presentation: A 20-year-old Greek man presented with high fever, appetite loss, nausea and vomiting, headache and significant malaise. He had an erythema of the palms and strikingly red lips and conjunctiva. As he did not respond to broad-spectrum antibiotics and after having excluded other possible diagnoses, the diagnosis of Kawasaki disease was set. He was treated with intravenous immunoglobulin and oral aspirin on the 10th day since the onset of the illness. His clinico-laboratory response was excellent and no coronary artery aneurysms were detected in coronary artery computed tomography performed 1 month later. Conclusions: This report of an adult case of European Kawasaki disease may be of benefit to physicians of various specialties, including primary care doctors, hospital internists, intensivists and cardiologists. It demonstrates that a case of prolonged fever, unresponsive to antibiotics, in the absence of other diagnoses may be an incident of Kawasaki disease. It is worth stressing that such a diagnosis should be considered, even if the patient is adult and not of Asian lineage

Recruitment of ubiquitin-activating enzyme UBA1 to DNA by poly(ADP-ribose) promotes ATR signalling

The DNA damage response (DDR) ensures cellular adaptation to genotoxic insults. In the crowded environment of the nucleus, the assembly of productive DDR complexes requires multiple protein modifications. How the apical E1 ubiquitin activation enzyme UBA1 integrates spatially and temporally in the DDR remains elusive. Using a human cell-free system, we show that poly(ADP-ribose) polymerase 1 promotes the recruitment of UBA1 to DNA. We find that the association of UBA1 with poly(ADP-ribosyl)ated protein–DNA complexes is necessary for the phosphorylation replication protein A and checkpoint kinase 1 by the serine/threonine protein kinase ataxia-telangiectasia and RAD3-related, a prototypal response to DNA damage. UBA1 interacts directly with poly(ADP-ribose) via a solvent-accessible and positively charged patch conserved in the Animalia kingdom but not in Fungi. Thus, ubiquitin activation can anchor to poly(ADP-ribose)-seeded protein assemblies, ensuring the formation of functional ataxia-telangiectasia mutated and RAD3-related-signalling complexes

Use and misuse of temperature normalisation in meta-analyses of thermal responses of biological traits

There is currently unprecedented interest in quantifying variation in thermal physiology among organisms, especially in order to understand and predict the biological impacts of climate change. A key parameter in this quantification of thermal physiology is the performance or value of a rate, across individuals or species, at a common temperature (temperature normalisation). An increasingly popular model for fitting thermal performance curves to data—the Sharpe-Schoolfield equation—can yield strongly inflated estimates of temperature-normalised rate values. These deviations occur whenever a key thermodynamic assumption of the model is violated, i.e., when the enzyme governing the performance of the rate is not fully functional at the chosen reference temperature. Using data on 1,758 thermal performance curves across a wide range of species, we identify the conditions that exacerbate this inflation. We then demonstrate that these biases can compromise tests to detect metabolic cold adaptation, which requires comparison of fitness or rate performance of different species or genotypes at some fixed low temperature. Finally, we suggest alternative methods for obtaining unbiased estimates of temperature-normalised rate values for meta-analyses of thermal performance across species in climate change impact studies