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.

Cultural cooperation, institution building, and metropolitan governance in decentralizing Indonesia

The institutional turn in metropolitan governance has been influenced to a considerable degree by a rational choice approach, which views metropolitan governance as essentially created by local actors to reduce the transaction costs of inter-jurisdictional public-service provision. Another influential theoretical route follows a historical approach, which emphasizes the role of the state structure in producing formal institutions to enable governance at the regional level. Both approaches tend to be formalistic, simplistic and deterministic in nature, thus neglecting the dynamic interactions between the actors and their more informal, intangible, yet more basic, legitimate institutions, such as culture. This article examines the dynamic role of culture in metropolitan governance building in the context of decentralizing Indonesia. The analysis focuses on ‘best-practice’ experiences of metropolitan cooperation in greater Yogyakarta, where three neighbouring local governments known as Kartamantul have collaboratively performed cross-border infrastructure development to deal with the consequences of extended urbanization. We draw on sociological institutionalism to argue that building this metropolitan cooperation has its roots in the capacity of the actors to use and mobilize culture as a resource for collaborative action.