Four small puzzles that Rosetta doesn't solve

A complete macromolecule modeling package must be able to solve the simplest structure prediction problems. Despite recent successes in high resolution structure modeling and design, the Rosetta software suite fares poorly on deceptively small protein and RNA puzzles, some as small as four residues. To illustrate these problems, this manuscript presents extensive Rosetta results for four well-defined test cases: the 20-residue mini-protein Trp cage, an even smaller disulfide-stabilized conotoxin, the reactive loop of a serine protease inhibitor, and a UUCG RNA tetraloop. In contrast to previous Rosetta studies, several lines of evidence indicate that conformational sampling is not the major bottleneck in modeling these small systems. Instead, approximations and omissions in the Rosetta all-atom energy function currently preclude discriminating experimentally observed conformations from de novo models at atomic resolution. These molecular "puzzles" should serve as useful model systems for developers wishing to make foundational improvements to this powerful modeling suite.Comment: Published in PLoS One as a manuscript for the RosettaCon 2010 Special Collectio

Investigating the specificity of peptide adsorption on gold using molecular dynamics simulations

We report all-atom molecular dynamics simulations following adsorption of gold-binding and non-gold-binding peptides on gold surfaces modeled with dispersive interactions. We examine the dependence of adsorption on both identity of the amino acids and mobility of the peptides. Within the limitations of the approach, results indicate that when the peptides are solvated, adsorption requires both configurational changes and local flexibility of individual amino acids. This is achieved when peptides consist mostly of random coils or when their secondary structural motifs (helices, sheets) are short and connected by flexible hinges. In the absence of solvent, only affinity for the surface is required: mobility is not important. In combination, these results suggest the barrier to adsorption presented by displacement of water molecules requires conformational sampling enabled through mobility.Fundação para a Ciência e a Tecnologia (FCT) – Programa Operacional “Ciência , Tecnologia, Inovação” – SFRH/BPD/20555/2004/0GV

MicrobesOnline: an integrated portal for comparative and functional genomics

Since 2003, MicrobesOnline (http://www.microbesonline.org) has been providing a community resource for comparative and functional genome analysis. The portal includes over 1000 complete genomes of bacteria, archaea and fungi and thousands of expression microarrays from diverse organisms ranging from model organisms such as Escherichia coli and Saccharomyces cerevisiae to environmental microbes such as Desulfovibrio vulgaris and Shewanella oneidensis. To assist in annotating genes and in reconstructing their evolutionary history, MicrobesOnline includes a comparative genome browser based on phylogenetic trees for every gene family as well as a species tree. To identify co-regulated genes, MicrobesOnline can search for genes based on their expression profile, and provides tools for identifying regulatory motifs and seeing if they are conserved. MicrobesOnline also includes fast phylogenetic profile searches, comparative views of metabolic pathways, operon predictions, a workbench for sequence analysis and integration with RegTransBase and other microbial genome resources. The next update of MicrobesOnline will contain significant new functionality, including comparative analysis of metagenomic sequence data. Programmatic access to the database, along with source code and documentation, is available at http://microbesonline.org/programmers.html.United States. Dept. of Energy (Genomics: GTL program (grant DE-AC02-05CH11231)

A systematic review of the health and well-being benefits of biodiverse environments

This is an Accepted Manuscript of an article published by Taylor & Francis in the Journal of Toxicology and Environmental Health, Part B: Critical Reviews on 05 Mar 2014, available online: http://www.tandfonline.com/doi/pdf/10.1080/10937404.2013.856361Recent ecosystem service models have placed biodiversity as a central factor in the processes that link the natural environment to health. While it is recognized that disturbed ecosystems might negatively affect human well-being, it is not clear whether biodiversity is related to or can promote "good" human health and well-being. The aim of this study was to systematically identify, summarize, and synthesize research that had examined whether biodiverse environments are health promoting. The objectives were twofold: (1) to map the interdisciplinary field of enquiry and (2) to assess whether current evidence enables us to characterize the relationship. Due to the heterogeneity of available evidence a narrative synthesis approach was used, which is textual rather than statistical. Extensive searches identified 17 papers that met the inclusion criteria: 15 quantitative and 2 qualitative. The evidence was varied in disciplinary origin, with authors approaching the question using different study designs and methods, and conceptualizations of biodiversity, health, and well-being. There is some evidence to suggest that biodiverse natural environments promote better health through exposure to pleasant environments or the encouragement of health-promoting behaviors. There was also evidence of inverse relationships, particularly at a larger scale (global analyses). However, overall the evidence is inconclusive and fails to identify a specific role for biodiversity in the promotion of better health. High-quality interdisciplinary research is needed to produce a more reliable evidence base. Of particular importance is identifying the specific ecosystem services, goods, and processes through which biodiversity may generate good health and well-being.European Regional Development Fund Programme 2007 to 2013European Social Fund Convergence Programme for Cornwall and the Isles of Scilly

Superfamily Assignments for the Yeast Proteome through Integration of Structure Prediction with the Gene Ontology

Saccharomyces cerevisiae is one of the best-studied model organisms, yet the three-dimensional structure and molecular function of many yeast proteins remain unknown. Yeast proteins were parsed into 14,934 domains, and those lacking sequence similarity to proteins of known structure were folded using the Rosetta de novo structure prediction method on the World Community Grid. This structural data was integrated with process, component, and function annotations from the Saccharomyces Genome Database to assign yeast protein domains to SCOP superfamilies using a simple Bayesian approach. We have predicted the structure of 3,338 putative domains and assigned SCOP superfamily annotations to 581 of them. We have also assigned structural annotations to 7,094 predicted domains based on fold recognition and homology modeling methods. The domain predictions and structural information are available in an online database at http://rd.plos.org/10.1371_journal.pbio.0050076_01

Environmental harm and environmental victims: scoping out a ‘green victimology'

In this paper I intend to discuss the adaptability of victimological study to the question of ‘environmental victimisation’. The impact on those affected by environment crime, or other environmentally damaging activities, is one that has received scarce attention in the mainstream victimological literature (see Williams, 1996). The role or position of such victims in criminal justice and/or other processes has likewise rarely been topic of academic debate. I have recently expanded upon various aspects of this subject and surrounding issues at greater length (Hall, 2013) but for the purposes of this article I wish to expand specifically on what a so-called ‘green victimology’ might look like, together with some of the particular questions and challenges it will face

Facing loss:Pedagogy of death

Loss, impermanence, and death are facts of life difficult to face squarely. Our own mortality and that of loved ones feels painful and threatening, the mortality of the biosphere unthinkable. Consequently, we do our best to dodge these thoughts, and the current globalizing culture supports and colludes in our evasiveness. Even environmental educators tend to foreground 'sustainability' whilst sidelining the reality of decline, decay, and loss. And yet, human life and ecological health require experiencing 'unsustainability' too, and a pedagogy for life requires a pedagogy of death. In this paper we explore experiences of loss and dying in both human relationships and the natural world through four different types of death affording situations, the cemetery, caring-unto-death, sudden death, and personal mortality. We trace the confluence of death in nature and human life, and consider some pedagogical affordance within and between these experiences as an invitation to foster an honest relationship with the mortality of self, others, and nature. We end by suggesting art as an ally in this reconnaissance, which can scaffold teaching and learning and support us to courageously accept both the beauty and the ugliness that death delivers to life

Using Human Disease Outbreaks as a Guide to Multilevel Ecosystem Interventions

Human health often depends on environmental variables and is generally subject to widespread and comprehensive surveillance. Compared with other available measures of ecosystem health, human disease incidence may be one of the most useful and practical bioindicators for the often elusive gauge of ecologic well-being. We argue that many subtle ecosystem disruptions are often identified only as a result of detailed epidemiologic investigations after an anomalous increase in human disease incidence detected by routine surveillance mechanisms. Incidence rates for vector-mediated diseases (e.g., arboviral illnesses) and direct zoonoses (e.g., hantaviruses) are particularly appropriate as bioindicators to identify underlying ecosystem disturbances. Outbreak data not only have the potential to act as a pivotal warning system for ecosystem disruption, but may also be used to identify interventions for the preservation of ecologic health. With this approach, appropriate ecologically based strategies for remediation can be introduced at an earlier stage than would be possible based solely on environmental monitoring, thereby reducing the level of “ecosystem distress” as well as resultant disease burden in humans. This concept is discussed using local, regional, and global examples, thereby introducing the concept of multilevel ecosystem interventions

Biodiversity, traditional medicine and public health: where do they meet?

Given the increased use of traditional medicines, possibilities that would ensure its successful integration into a public health framework should be explored. This paper discusses some of the links between biodiversity and traditional medicine, and addresses their implications to public health. We explore the importance of biodiversity and ecosystem services to global and human health, the risks which human impacts on ecosystems and biodiversity present to human health and welfare