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.

“I’m Not Waving, I’m Drowning”: An Autoethnographical Exploration of Biographical Disruption and Reconstruction During Recovery From Prescribed Benzodiazepine Use

Benzodiazepines are group of drugs used mainly as sedatives, hypnotics, muscle relaxants, and anti-epileptics. Tapering off benzodiazepines is, for some users, a painful, traumatic, and protracted process. In this article, I use an autoethnographic approach, adopting the metaphor of water, to examine heuristically my experience of iatrogenic illness and recovery. I draw on personal journals and blog entries and former users’ narratives to consider the particular form of biographical disruption associated with benzodiazepines and the processes involved in identity reconstruction. I emphasize the role of the online community in providing benzodiazepine users such as myself with a co-cultural community through which to share a voice and make sense of our experiences. I explain how the success stories of former users provided me with the hope that I, the “medical victim,” could become the “victor” and in the process construct a new life and fresh identity.