Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies

The evolution of enzymes affects how well a species can adapt to new environmental conditions. During enzyme evolution, certain aspects of molecular function are conserved while other aspects can vary. Aspects of function that are more difficult to change or that need to be reused in multiple contexts are often conserved, while those that vary may indicate functions that are more easily changed or that are no longer required. In analogy to the study of conservation patterns in enzyme sequences and structures, we have examined the patterns of conservation and variation in enzyme function by analyzing graph isomorphisms among enzyme substrates of a large number of enzyme superfamilies. This systematic analysis of substrate substructures establishes the conservation patterns that typify individual superfamilies. Specifically, we determined the chemical substructures that are conserved among all known substrates of a superfamily and the substructures that are reacting in these substrates and then examined the relationship between the two. Across the 42 superfamilies that were analyzed, substantial variation was found in how much of the conserved substructure is reacting, suggesting that superfamilies may not be easily grouped into discrete and separable categories. Instead, our results suggest that many superfamilies may need to be treated individually for analyses of evolution, function prediction, and guiding enzyme engineering strategies. Annotating superfamilies with these conserved and reacting substructure patterns provides information that is orthogonal to information provided by studies of conservation in superfamily sequences and structures, thereby improving the precision with which we can predict the functions of enzymes of unknown function and direct studies in enzyme engineering. Because the method is automated, it is suitable for large-scale characterization and comparison of fundamental functional capabilities of both characterized and uncharacterized enzyme superfamilies

Rapid detection of similarity in protein structure and function through contact metric distances

The characterization of biological function among newly determined protein structures is a central challenge in structural genomics. One class of computational solutions to this problem is based on the similarity of protein structure. Here, we implement a simple yet efficient measure of protein structure similarity, the contact metric. Even though its computation avoids structural alignments and is therefore nearly instantaneous, we find that small values correlate with geometrical root mean square deviations obtained from structural alignments. To test whether the contact metric detects functional similarity, as defined by Gene Ontology (GO) terms, it was compared in large-scale computational experiments to four other measures of structural similarity, including alignment algorithms as well as alignment independent approaches. The contact metric was the fastest method and its sensitivity, at any given specificity level, was a close second only to Fast Alignment and Search Tool—a structural alignment method that is slower by three orders of magnitude. Critically, nearly 40% of correct functional inferences by the contact metric were not identified by any other approach, which shows that the contact metric is complementary and computationally efficient in detecting functional relationships between proteins. A public ‘Contact Metric Internet Server’ is provided

Literary studies and the academy

In 1885 the University of Oxford invited applications for the newly created Merton Professorship of English Language and Literature. The holder of the chair was, according to the statutes, to ‘lecture and give instruction on the broad history and criticism of English Language and Literature, and on the works of approved English authors’. This was not in itself a particularly innovatory move, as the study of English vernacular literature had played some part in higher education in Britain for over a century. Oxford University had put English as a subject into its pass degree in 1873, had been participating since 1878 in extension teaching, of which literary study formed a significant part, and had since 1881 been setting special examinations in the subject for its non-graduating women students. What was new was the fact that this ancient university appeared to be on the verge of granting the solid academic legitimacy of an established chair to an institutionally marginal and often contentious intellectual pursuit, acknowledging the study of literary texts in English to be a fit subject not just for women and the educationally disadvantaged but also for university men

Spatio-statistical Predictions of Vernal Pool Locations in Massachusetts: Incorporating the Spatial Component into Ecological Modeling

Vernal pools are small, isolated, depressions that experience cyclical periods of inundation and drying. Many species have evolved strategies to utilize the unique characteristics of vernal pools; however, their small size, seasonal nature, and isolation from other, larger water bodies, suggest increased risk of damage or loss by development. The objectives of this research were to statistically determine physical predictors of vernal pool presence, and subsequently, to represent the output cartographically for use as a conservation tool. Logistic regression and Classification and Regression Tree (CART) methods were used to identify important predictors of 405 known vernal pools across northeastern Massachusetts. The CART models performed most favorably, achieving map accuracies as high as 97 percent and providing a set of rules for vernal pool prediction. It is important to note that we observed significant discrepancies between model accuracy and map accuracy, illustrating the pitfall of relying on statistical metrics alone (e.g., R2 values) to assess the quality of spatial analyses

The Sustainable Groundwater Management Act and the Common Law of Groundwater Rights—Finding a Consistent Path Forward for Groundwater Allocation

In 2014, the California State Legislature enacted the Sustainable Groundwater Management Act (SGMA), which requires the formation of new local agencies, known as Groundwater Sustainability Agencies (GSAs), to sustainably manage groundwater basins throughout the state.  The statute represents the first statewide framework for groundwater management in California.  Among other tasks, GSAs, especially those in overdrafted basins, will have to allocate available water among users and set up systems to hold pumpers to their allocated limit.  However, SGMA did not change the longstanding framework of groundwater pumping rights established by California courts.  This sets up the possibility of conflict between groundwater allocation plans adopted by GSAs and water rights.This Article analyzes the relationship between SGMA and water rights under the common law.  It identifies a path for GSAs to allocate groundwater and limit pumping in a manner best situated to sustain judicial scrutiny.  We examine how the common law defines water right priorities for groundwater pumping allocations, as well as areas where the common law provides flexibility.  This flexibility allows for creativity in arriving at allocations that fit stakeholders’ goals for both sustainable and smart water management.  We seek to help GSAs reduce the risk of litigation and increase the likelihood their Groundwater Sustainability Plan (GSP) will survive litigation, without judicial modification.  There are considerable measures GSAs can take to manage their litigation risk and enhance the durability of their GSPs, including making groundwater allocations in their GSPs consistent with the principles of water rights and seeking consensus among affected stakeholders.  We also seek to provide a framework for courts to work out the appropriate relationship between SGMA and the common law of water rights when litigation occurs