EDULISS: a small-molecule database with data-mining and pharmacophore searching capabilities

We present the relational database EDULISS (EDinburgh University Ligand Selection System), which stores structural, physicochemical and pharmacophoric properties of small molecules. The database comprises a collection of over 4 million commercially available compounds from 28 different suppliers. A user-friendly web-based interface for EDULISS (available at http://eduliss.bch.ed.ac.uk/) has been established providing a number of data-mining possibilities. For each compound a single 3D conformer is stored along with over 1600 calculated descriptor values (molecular properties). A very efficient method for unique compound recognition, especially for a large scale database, is demonstrated by making use of small subgroups of the descriptors. Many of the shape and distance descriptors are held as pre-calculated bit strings permitting fast and efficient similarity and pharmacophore searches which can be used to identify families of related compounds for biological testing. Two ligand searching applications are given to demonstrate how EDULISS can be used to extract families of molecules with selected structural and biophysical features

Software platform virtualization in chemistry research and university teaching

<p>Abstract</p> <p>Background</p> <p>Modern chemistry laboratories operate with a wide range of software applications under different operating systems, such as Windows, LINUX or Mac OS X. Instead of installing software on different computers it is possible to install those applications on a single computer using Virtual Machine software. Software platform virtualization allows a single guest operating system to execute multiple other operating systems on the same computer. We apply and discuss the use of virtual machines in chemistry research and teaching laboratories.</p> <p>Results</p> <p>Virtual machines are commonly used for cheminformatics software development and testing. Benchmarking multiple chemistry software packages we have confirmed that the computational speed penalty for using virtual machines is low and around 5% to 10%. Software virtualization in a teaching environment allows faster deployment and easy use of commercial and open source software in hands-on computer teaching labs.</p> <p>Conclusion</p> <p>Software virtualization in chemistry, mass spectrometry and cheminformatics is needed for software testing and development of software for different operating systems. In order to obtain maximum performance the virtualization software should be multi-core enabled and allow the use of multiprocessor configurations in the virtual machine environment. Server consolidation, by running multiple tasks and operating systems on a single physical machine, can lead to lower maintenance and hardware costs especially in small research labs. The use of virtual machines can prevent software virus infections and security breaches when used as a sandbox system for internet access and software testing. Complex software setups can be created with virtual machines and are easily deployed later to multiple computers for hands-on teaching classes. We discuss the popularity of bioinformatics compared to cheminformatics as well as the missing cheminformatics education at universities worldwide.</p

Development and validation of an improved algorithm for overlaying flexible molecules

A program for overlaying multiple flexible molecules has been developed. Candidate overlays are generated by a novel fingerprint algorithm, scored on three objective functions (union volume, hydrogen-bond match, and hydrophobic match), and ranked by constrained Pareto ranking. A diverse subset of the best ranked solutions is chosen using an overlay-dissimilarity metric. If necessary, the solutions can be optimised. A multi-objective genetic algorithm can be used to find additional overlays with a given mapping of chemical features but different ligand conformations. The fingerprint algorithm may also be used to produce constrained overlays, in which user-specified chemical groups are forced to be superimposed. The program has been tested on several sets of ligands, for each of which the true overlay is known from protein–ligand crystal structures. Both objective and subjective success criteria indicate that good results are obtained on the majority of these sets

Viral ecogenomics across the Porifera

BackgroundViruses directly affect the most important biological processes in the ocean via their regulation of prokaryotic and eukaryotic populations. Marine sponges form stable symbiotic partnerships with a wide diversity of microorganisms and this high symbiont complexity makes them an ideal model for studying viral ecology. Here, we used morphological and molecular approaches to illuminate the diversity and function of viruses inhabiting nine sponge species from the Great Barrier Reef and seven from the Red Sea.ResultsViromic sequencing revealed host-specific and site-specific patterns in the viral assemblages, with all sponge species dominated by the bacteriophage order Caudovirales but also containing variable representation from the nucleocytoplasmic large DNA virus families Mimiviridae, Marseilleviridae, Phycodnaviridae, Ascoviridae, Iridoviridae, Asfarviridae and Poxviridae. Whilst core viral functions related to replication, infection and structure were largely consistent across the sponge viromes, functional profiles varied significantly between species and sites largely due to differential representation of putative auxiliary metabolic genes (AMGs) and accessory genes, including those associated with herbicide resistance, heavy metal resistance and nylon degradation. Furthermore, putative AMGs varied with the composition and abundance of the sponge-associated microbiome. For instance, genes associated with antimicrobial activity were enriched in low microbial abundance sponges, genes associated with nitrogen metabolism were enriched in high microbial abundance sponges and genes related to cellulose biosynthesis were enriched in species that host photosynthetic symbionts.ConclusionsOur results highlight the diverse functional roles that viruses can play in marine sponges and are consistent with our current understanding of sponge ecology. Differential representation of putative viral AMGs and accessory genes across sponge species illustrate the diverse suite of beneficial roles viruses can play in the functional ecology of these complex reef holobionts

Local identity in the form production process, using as a case study the multifunctional administrative city project (Sejong) in South Korea

This article argues that many of those changes to the built environment brought about through economic and cultural globalization have resulted in a blurring of national identities expressed through city form, worldwide, including South East and Far East Asian countries. As a reaction to this, local identity has emerged as a central concern among both academics and many built environment professionals for setting the twenty-first century urban development agenda. The focus of this article is to explore place-making in relation to the role of different actors within the form-production process, and the implications of globalization for local identity using as a case the new multifunctional administrative city of Sejong in South Korea. Evidence was collected using a testing survey that aimed at gaining a clear insight into the role of local identity from the perspectives of different key actors involved in the Sejong project; the survey focused on building up a comprehensive narrative of their knowledge, experience, and sense of identity and sustainability in relation to place identity in new place construction. This survey and the findings from it illustrate the importance of user participation in the decision-making process, in achieving social sustainability and the incorporation of local cultural resources. The findings summarized in this article reveal the current poor level of understanding and the limitations in delivering inclusive local identity within the urban design policies of Sejong, and how local identity and the needs of local culture could be incorporated, sustained and developed in contemporary new town development in the South East/Far East Asian context

Katalytische Hydrierung von Stickstoffhaltigen Heterocyclen. V. Hydrierung von Benzoxazolen

Die kataly1ri.sche Hydrierung von 2-Methyl- (I) und 2-Phenyl- benzoxazol (II) wurde mittels verschiedener Katalysatoren U!Iltersucht. In Eisessig an Platin nach Adams, bei Normaldruck U!Ild Raumtemperatur, oder an Rhodium/Kohle Katalysator bei 50 Atu U!Ild 60 °C wurden I und II unter Absattigung der Benzolkeme und Hydrogenolyse der 1-5 Bilndung des Oxazolringes den zu Ami:den III und IV hydriert. Die Hidrierung gelang ausserdem nocht mit einem Rhoclium-Platiln (4 : 1) Mischkatalysator; Pd/BaS04; Haney- Nic~el sowie NaBH4 als Reduktionsmittel waren ·tnalcliv. Bei der Hydrierung von N-(2-Hydroxy-phenyl)-acetamid (V) an Rhodium/ /Kohle bei erhohtem Druck und -erhohter Temperatur gewann man in 800/o-iger Ausbeute das cis-N-(2-Hydrnxy-cyclohexyl)-acetamid (VI)

Correlation and prediction of a large blood-brain distribution data set - an LFER study

We report linear free energy relation (LFER) models of the equilibrium distribution of molecules between blood and brain, as log BB values. This method relates log BB values to fundamental molecular properties, such as hydrogen bonding capability, polarity/polarisability and size. Our best model of this form covers 148 compounds, the largest set of log BB data yet used in such a model, resulting in R2=0.745 and e.s.d.=0.343 after inclusion of an indicator variable for carboxylic acids. This represents rather better accuracy than a number of previously reported models based on subsets of our data. The model also reveals the factors that affect log BB: molecular size and dispersion effects increase brain uptake, while polarity/polarisability and hydrogen-bond acidity and basicity decrease it. By splitting the full data set into several randomly selected training and test sets, we conclude that such a model can predict log BB values with an accuracy of less than 0.35 log units. The method is very rapid—log BB can be calculated from structure at a rate of 700 molecules per minute on a silicon graphics O2