Development of user-friendly, high throughput screening for ligands and inhibitors of carbohydrate modifying enzymes

This paper describes the impact of cloud computing and the use of GPUs on the performance of Autodock and Gromacs respectively. Cloud computing was applicable to reducing the ‘‘tail’’ seen in running Autodock on desktop grids and the GPU version of Gromacs showed significant improvement over the CPU version. A large (200,000 compounds) library of small molecules, seven sialic acid analogues of the putative substrate and 8000 sugar molecules were converted into pdbqt format and used to interrogate the Trichomonas vaginalis neuraminidase using Autodock Vina. Good binding energy was noted for some of the small molecules (~-9 kcal/mol), but the sugars bound with affinity of less than -7.6 kcal/mol. The screening of the sugar library resulted in a ‘‘top hit’’ with a-2,3-sialyllacto-N-fucopentaose III, a derivative of the sialyl Lewisx structure and a known substrate of the enzyme. Indeed in the top 100 hits 8 were related to this structure. A comparison of Autodock Vina and Autodock 4.2 was made for the high affinity small molecules and in some cases the results were superimposable whereas in others, the match was less good. The validation of this work will require extensive ‘‘wet lab’’ work to determine the utility of the workflow in the prediction of potential enzyme inhibitors.

Is childhood a 'disability'? Exploring the exclusion of children from age discrimination provisions in the Equality Act 2010

The Equality Act 2010 was enacted with the aim of simplifying existing equality legislation and included extending age discrimination protection beyond the workplace to cover the provision of goods, facilities and services. Under-18s, however, were omitted from such provisions, despite lobbying from a number of different organisations and parliamentarians. This article considers the significance of this exclusion. It both challenges the legitimacy of the decision to exclude children, and considers the difficulties that arise from including under-18s within age discrimination provisions, namely those relating to children’s autonomy, capacity and right to equal treatment. In particular, it asks whether the question of children’s capacity to make decisions, the main ground on which children are denied all the human rights enjoyed by adults, should be revisited in light of the adoption of the Convention on the Rights of Persons with Disabilities, under which a finding of incapacity on the basis of disability constitutes discrimination. It goes on to explore other areas of convergence between childhood and disability studies, and particularly the benefits, and shortcomings, of a ‘social model’ approach to childhood.