Dissecting water binding sites at protein–protein interfaces: a lesson from the atomic structures in the Protein Data Bank

We dissect the protein–protein interfaces into water preservation (WP), water hydration (WH) and water dehydration (WD) sites by comparing the water-mediated hydrogen bonds (H-bond) in the bound and unbound states of the interacting subunits. Upon subunit complexation, if a H-bond between an interface water and a protein polar group is retained, we assign it as WP site; if it is lost, we assign it as WD site and if a new H-bond is created, we assign it as WH site. We find that the density of WD sites is highest followed by WH and WP sites except in antigen and (or) antibody complexes, where the density of WH sites is highest followed by WD and WP sites. Furthermore, we find that WP sites are the most conserved followed by WD and WH sites in all class of complexes except in antigen and (or) antibody complexes, where WD sites are the most conserved followed by WH and WP sites. A significant number of WP and WH sites are involved in water bridges that stabilize the subunit interactions. At WH sites, the residues involved in water bridges are significantly better conserved than the other residues. However, no such difference is observed at WP sites. Interestingly, WD sites are generally replaced with direct H-bonds upon subunit complexation. Significantly, we observe many water-mediated H-bonds remain preserved in spite of large conformational changes upon subunit complexation. These findings have implications in predicting and engineering water binding sites at protein–protein interfaces.     

Have we seen all structures corresponding to short protein fragments in the Protein Data Bank? An update

Assembling short fragments from known structures has been a widely used approach to construct novel protein structures. To what extent there exist structurally similar fragments in the database of known structures for short fragments of a novel protein is a question that is fundamental to this approach. This work addresses that question for seven-, nine- and 15-residue fragments. For each fragment size, two databases, a query database and a template database of fragments from high-quality protein structures in SCOP20 and SCOP90, respectively, were constructed. For each fragment in the query database, the template database was scanned to find the lowest r.m.s.d. fragment among non-homologous structures. For seven-residue fragments, there is a 99% probability that there exists such a fragment within 0.7 A r.m.s.d. for each loop fragment. For nine-residue fragments there is a 96% probability of a fragment within 1 A r.m.s.d., while for 15-residue fragments there is a 91% probability of a fragment within 2 A r.m.s.d. These results, which update previous studies, show that there exists sufficient coverage to model even a novel fold using fragments from the Protein Data Bank, as the current database of known structures has increased enormously in the last few years. We have also explored the use of a grid search method for loop homology modeling and make some observations about the use of a grid search compared with a database search for the loop modeling problem.     

Protein–ligand interactions: Probing the energetics of a putative cation–π interaction

In order to probe the energetics associated with a putative cation–π interaction, thermodynamic parameters are determined for complex formation between the Grb2 SH2 domain and tripeptide derivatives of RCO–pTyr–Ac6c–Asn wherein the R group is varied to include different alkyl, cycloalkyl, and aryl groups. Although an indole ring is reputed to have the strongest interaction with a guanidinium ion, binding free energies, ΔG°, for derivatives of RCO–pTyr–Ac6c–Asn bearing cyclohexyl and phenyl groups were slightly more favorable than their indolyl analog. Crystallographic analysis of two complexes reveals that test ligands bind in similar poses with the notable exception of the relative orientation and proximity of the phenyl and indolyl rings relative to an arginine residue of the domain. These spatial orientations are consistent with those observed in other cation–π interactions, but there is no net energetic benefit to such an interaction in this biological system. Accordingly, although cation–π interactions are well documented as important noncovalent forces in molecular recognition, the energetics of such interactions may be mitigated by other nonbonded interactions and solvation effects in protein–ligand associations.     

SPdb – a signal peptide database

Background  

The signal peptide plays an important role in protein targeting and protein translocation in both prokaryotic and eukaryotic cells. This transient, short peptide sequence functions like a postal address on an envelope by targeting proteins for secretion or for transfer to specific organelles for further processing. Understanding how signal peptides function is crucial in predicting where proteins are translocated. To support this understanding, we present SPdb signal peptide database , a repository of experimentally determined and computationally predicted signal peptides.     

The glomerulus – a view from the outside – the podocyte

In the past decade, podocyte research has been greatly aided by the development of powerful new molecular, cellular and animal tools, leading to elucidation of an increasing number of proteins involved in podocyte function and identification of mutated genes in hereditary glomerulopathies. Accumulating evidence indicates that podocyte disorders may not only underlie these hereditary glomerulopathies but also play crucial role in a broad spectrum of acquired glomerular diseases. Genetic susceptibility, environmental influence and systemic responses are all involved in the mediation of the pathogenesis of podocytopathies. Injured podocytes may predisopose to further injury of other podocytes and other adjacent/distant renal cells in a vicious cycle, leading to inexorable progression of glomerular injury. The classic view is that podocytes have a limited ability to proliferate in the normal mature kidney. However, recent research in rodents has provided suggestive evidence for podocyte regeneration resulting from differentiation of progenitor cells within Bowman's capsule.     

Data envelopment analysis of cities – Investigation of the ecological and economic efficiency of cities using a benchmarking concept from production management

To better understand the economic performance of cities and the accompanying social and environmental implications, one focus of research has been on ways to quantify performance advantages of growth and size while considering the impact of economies of scale. An important aspect of the current discussion is the introduction of the merely environmental driven concept of resource efficiency, defined as minimizing resource consumption while enhancing the quality of life. However, as yet there is no commonly agreed method on how best to measure efficiency. In order to contribute to this debate, an approach is described here of applying Data Envelopment Analysis (DEA) to study the resource efficiency of cities. Originating in the field of economics, DEA is a non-parametric, deterministic method to measure the efficiency of economic production, specifically the relative efficiency of Decision Making Units (DMUs).Here we test the usefulness of DEA to analyze urban efficiency by applying it to an investigation of 116 cities throughout Germany. This entailed the development of two separate economic and ecological models in order to allow more precise identification of the relevance of individual parameters during the evaluation process. The results allow a ranking of cities as well as an estimation of the ratios of economic and ecological efficiencies of the investigated cities, realized with the aid of a nine-field matrix (portfolio).DEA is at the same time a promising heuristic tool to help draw the basic outlines of a resource efficient city and to shed light on the underlying factors that boost or reduce efficiency. We recommend a three-step approach. First, two separate models should be defined (ecological, economic) and used to feed the DEA computation. Second, the results are spread in a portfolio to give an overview of the ecological and economic efficiency scores. This provides a basic overview of the DEA results for the selected cities following a basic and abstract model without determination of causal relationships between these values. Third, the field-dependent commonalities between the cities are considered. Additional indicators that also characterize the selected cities (but which were not selected as inputs to the algorithm) can now be examined. In this way, it is possible to understand the common factors that determine the level of efficiency as well as to learn about the qualitative difference and specific features of cities in the particular matrix quadrants.     

Macroecology in the age of Big Data – Where to go from here?

Recent years have seen an exponential increase in the amount of data available in all sciences and application domains. Macroecology is part of this “Big Data” trend, with a strong rise in the volume of data that we are using for our research. Here, we summarize the most recent developments in macroecology in the age of Big Data that were presented at the 2018 annual meeting of the Specialist Group Macroecology of the Ecological Society of Germany, Austria and Switzerland (GfÖ). Supported by computational advances, macroecology has been a rapidly developing field over recent years. Our meeting highlighted important avenues for further progress in terms of standardized data collection, data integration, method development and process integration. In particular, we focus on (a) important data gaps and new initiatives to close them, for example through space- and airborne sensors, (b) how various data sources and types can be integrated, (c) how uncertainty can be assessed in data-driven analyses and (d) how Big Data and machine learning approaches have opened new ways of investigating processes rather than simply describing patterns. We discuss how Big Data opens up new opportunities, but also poses new challenges to macroecological research. In the future, it will be essential to carefully assess data quality, the reproducibility of data compilation and analytical methods, and the communication of uncertainties. Major progress in the field will depend on the definition of data standards and workflows for macroecology, such that scientific quality and integrity are guaranteed, and collaboration in research projects is made easier.     

CLO-PLA2 – a database of clonal plants in central Europe

CLO-PLA2' (CLOnal PLAnts, version 2) is a database on architectural aspects of clonal growth in vascular plants of central Europe. The database includes 2749 species, characterised by 25 variables, either directly or indirectly related to clonal growth. The total number of items in the database is over 12750. The structure of the database is described and the variables used to characterise clonal growth of individual species are listed. Two examples of database utilisation are given. The first concerns the relationship between habitat niche width and the mode of clonal growth. Turf graminoids, species with long-lived rhizomes either short to long and formed below-ground, or short and formed above-ground, and short-lived rhizomes formed above-ground, are over-represented among the species with very broad niches and under-represented among the species with narrow niches. In contrast, species multiplying by plant fragments are missing among the species with the broadest niches. The second example explores how individual clonal growth modes are combined in individual species. About 21% of species of clonal plants have more than one mode of clonal growth. Some combinations are over-represented in certain families and environments. The application of phylogenetic independent contrasts (PIC) showed that both phylogenetic constraints and adaptations to particular environmental conditions play important roles in determining the observed pattern.     

Recommendations for the presentation of NMR structures of proteins and nucleic acids – IUPAC-IUBMB-IUPAB Inter-Union Task Group on the Standardization of Data Bases of Protein and Nucleic Acid Structures Determined by NMR Spectroscopy

The recommendations presented here are designed to support easier communication of NMR data and NMR structures of proteins and nucleic acids through unified nomenclature and reporting standards. Much of this document pertains to the reporting of data in journal articles; however, in the interest of the future development of structural biology, it is desirable that the bulk of the reported information be stored in computer-accessible form and be freely accessible to the scientific community in standardized formats for data exchange. These recommendations stem from an IUPAC-IUBMB-IUPAB inter-union venture with the direct involvement of ICSU and CODATA. The Task Group has reviewed previous formal recommendations and has extended them in the light of more recent developments in the field of biomolecular NMR spectroscopy. Drafts of the recommendations presented here have been examined critically by more than 50 specialists in the field and have gone through two rounds of extensive modification to incorporate suggestions and criticisms.     

The glomerulus – a view from the inside – the endothelial cell

The glomerular endothelial cells are unique both in location and anatomy compared to most other endothelial cells throughout the body. The absence of a diaphragm with retention of a basement membrane and fenestrations enable these uniquely situated cells to have a key role in filtration performed by the kidney. Interaction with other glomerular cells such as the podocytes and mesangial cells, as well as with circulating and infiltrating inflammatory cells, contribute to the final impact of the glomerular endothelial cells on maintenance of body fluid homeostasis and modulation of disease. Thus, endothelial cells contribute to hemodynamic function, reactive oxygen stress, regulate the balance between pro-thrombotic and anti-thrombotic forces, and importantly, contribute to fibrosis, the key injury of progressive chronic kidney disease. Repair of endothelial cell damage and restoration of segmentally sclerosed glomeruli are key areas considered for intervention in chronic kidney disease. This review will focus on the structure, function, and interplay of endothelial cells with other glomerular cells and systemic factors, their impact on renal disease and give rationale for possible intervention that may forestall progressive injuries.     

Automated hexahedral meshing of knee cartilage structures – application to data from the osteoarthritis initiative

We propose a fully automated methodology for hexahedral meshing of patient-specific structures of the human knee obtained from magnetic resonance images, i.e. femoral/tibial cartilages and menisci. We select eight patients from the Osteoarthritis Initiative and validate our methodology using MATLAB on a laptop computer. We obtain the patient-specific meshes in an average of three minutes, while faithfully representing the geometries with well-shaped elements. We hope to provide a fundamentally different means to test hypotheses on the mechanisms of disease progression by integrating our patient-specific FE meshes with data from individual patients. Download both our meshes and software at http://im.engr.uconn.edu/downloads.php.     

INDIGO – INtegrated Data Warehouse of MIcrobial GenOmes with Examples from the Red Sea Extremophiles

Background

The next generation sequencing technologies substantially increased the throughput of microbial genome sequencing. To functionally annotate newly sequenced microbial genomes, a variety of experimental and computational methods are used. Integration of information from different sources is a powerful approach to enhance such annotation. Functional analysis of microbial genomes, necessary for downstream experiments, crucially depends on this annotation but it is hampered by the current lack of suitable information integration and exploration systems for microbial genomes.

Results

We developed a data warehouse system (INDIGO) that enables the integration of annotations for exploration and analysis of newly sequenced microbial genomes. INDIGO offers an opportunity to construct complex queries and combine annotations from multiple sources starting from genomic sequence to protein domain, gene ontology and pathway levels. This data warehouse is aimed at being populated with information from genomes of pure cultures and uncultured single cells of Red Sea bacteria and Archaea. Currently, INDIGO contains information from Salinisphaera shabanensis, Haloplasma contractile, and Halorhabdus tiamatea - extremophiles isolated from deep-sea anoxic brine lakes of the Red Sea. We provide examples of utilizing the system to gain new insights into specific aspects on the unique lifestyle and adaptations of these organisms to extreme environments.

Conclusions

We developed a data warehouse system, INDIGO, which enables comprehensive integration of information from various resources to be used for annotation, exploration and analysis of microbial genomes. It will be regularly updated and extended with new genomes. It is aimed to serve as a resource dedicated to the Red Sea microbes. In addition, through INDIGO, we provide our Automatic Annotation of Microbial Genomes (AAMG) pipeline. The INDIGO web server is freely available at http://www.cbrc.kaust.edu.sa/indigo.     

Skin Donors Positive for HBV Core Antibodies – to Bank or Not to Bank? An Overview from a Regional Tissue Bank

A prompt transplantation of skin allografts on patients with severe, large body area burns is a preferred treatment, but depends on a suitable supply of tissue donors. Limiting factors include donors' identification, families consent, and following the standards – exclusion due to assessed transmissible diseases. To increase the current rate of skin donations to our regional skin bank, we reviewed the data of all potential organ donors, identified at Soroka University Medical Center from October 1997 to December 2000 and evaluated the causes for exclusion, especially due to HBV serological profile. 114/168 (67.9%) patients did not meet the indicated standards for organ donation, among which 20/114 patients (17.5%) positive for anti-HBc (anti-HBc⁺). 54/168 persons were declared brain dead, with consents obtained from 21 families. To discuss the intriguing approval of skin from potential donors with anti-HBc⁺ serology, the literature was reviewed, specifically – the reported outcomes of organ transplants from anti-HBc⁺ donors, updates of HBV and skin, available tests, and finally a look for a safe commendable algorithm. The results suggested that HBV might be replicating in the skin, but proven communication of HBV has not been reported following grafting skin from anti-HBc⁺ donors. Unlike other procured organs and tissues, grafted banked skin is a temporary cover, storable up to six years, under appropriate conditions. Hence, banking of skin from anti-HBc⁺ donors might be considered for future grafting of patients with identical serological profiles, presumably immune to a subsequent HBV infection, until a further re-evaluation of the standards. This procedure is anticipated to increase the potential of organ and tissue donations, specifically skin.     

Bacterial Contamination of Tissue Allografts – Experiences of the Donor Tissue Bank of Victoria

The aim of this study is to report the experience of the Donor Tissue Bank of Victoria with bacteria isolated from musculoskeletal, skin and cardiac allografts retrieved from cadaveric donors. The results of all quality control samples for bacterial culture, taken during retrieval and processing of allografts at the DTBV for a 12 month period, were extracted and analysed. It was found that 15.7% of skin, 15.1% of heart valves and 5.8% of musculoskeletal samples had positive culture results. The number and types of organisms isolated varied with tissue type. The most commonly isolated organisms were Staphylococcus species (including S. aureus). The identity of the isolate and the number of positive specimens from the same donor were considerations in the decision concerning the suitability of tissue for subsequent implantation.     

Organogold(I) complexes of a C2-symmetric diacetylide ligand derived from 1,1′-bi-2-naphthol

Alkynylgold(I) complexes incorporating a chiral binaphthyl group have been prepared. Bis(alkyne) reagents [rac-1,1′-C₂₀H₁₂-2,2′-(OCH₂CCH)₂] (1) and [rac-1,1′-C₂₀H₁₂-2,2′-(OC(O)CH₂CCH)₂] (2), react with [AuCl(SMe₂)] and base to give insoluble oligomeric alkynylgold(I) complexes [rac-1,1′-C₂₀H₁₂-2,2′-(OCH₂CCAu)₂]_n (3) and [rac-1,1′-C₂₀H₁₂-2,2′-(OC(O)CH₂CCAu)₂]_n (4), which react with phosphine or diphosphine ligands to give soluble complexes [rac-1,1′-C₂₀H₁₂-2,2′-(OCH₂CCAuPR₃)₂] (5), R = Ph or Cy, [rac-1,1′-C₂₀H₁₂-2,2′-(OCH₂CCAu)₂(Ph₂P(CH₂)_nPPh₂)] (6), or [rac-1,1′-C₂₀H₁₂-2,2′-(OC(O)CH₂CCAu)₂(Ph₂P(CH₂)_nPPh₂)] (7), with n = 3–5. Several of the complexes 6 and 7 are shown to exist as mixtures of isomeric forms in solution.     

PCAS – a precomputed proteome annotation database resource

Background  

Many model proteomes or "complete" sets of proteins of given organisms are now publicly available. Much effort has been invested in computational annotation of those "draft" proteomes. Motif or domain based algorithms play a pivotal role in functional classification of proteins. Employing most available computational algorithms, mainly motif or domain recognition algorithms, we set up to develop an online proteome annotation system with integrated proteome annotation data to complement existing resources.