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.

You Should Never Look a Gift Horse in the Mouth: One-Size-Fits-All Compensation in Wrongful Conception

This article reconsiders the House of Lords decision in Rees v. Darlington Memorial Hospital NHS Trust (2003) and the decision to award a conventional award of £15,000 in all cases of failed sterilisation resulting in the birth of an unwanted child. In so doing, it briefly recites the history of the Wrongful Conception action and the unique facts of Rees. It then goes on the consider the implications of two fundamental aspects of the judgment. Firstly, it looks at the 'conventional award' itself and considers the reasoning behind the award and the effect that it has on our understanding of (particularly women's) reproductive autonomy. Secondly, it analyses the rather 'unique' judgment of Lord Scott and his decision to evaluate these cases using the possessory analogy of an unwanted foal; particular focus is given to the notion of parental 'choice' in these cases and whether mitigation (i.e. abortion or adoption) can ever be considered "reasonable".