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E3 ligases are genetically implicated in many human diseases, yet E3 enzyme mechanisms are not fully understood, and there is a strong need for pharmacological probes of E3s. We report the discovery that the HECT E3 Nedd4-1 is a processive enzyme and that disruption of its processivity by biochemical mutations or small molecules switches Nedd4-1 from a(More)
A novel fragment-based drug discovery approach is reported which irreversibly tethers drug-like fragments to catalytic cysteines. We attached an electrophile to 100 fragments without significant alterations in the reactivity of the electrophile. A mass spectrometry assay discovered three nonpeptidic inhibitors of the cysteine protease papain. The identified(More)
Clustering algorithm is applied to many fields, especially in the data mining. Due to the increasing number of the data, it's too hard for the clustering algorithm to afford the computation time in traditional computing model. When handling with big data, the corresponding algorithms of data mining have been transformed from the original single-core or(More)
Cloud computing can provide the dynamic and elastic virtual resources for the users to execute the large-scale computing tasks. It has become the hot spot in the academic and industry fields. The tasks scheduling plays an important role in the Cloud computing. It should adopt the scheme to dispatch the computing tasks to the appropriate resources(More)
Rhodesain, the major cathepsin L-like cysteine protease in the protozoan Trypanosoma brucei rhodesiense, the causative agent of African sleeping sickness, is a well-validated drug target. In this work, we used a fragment-based approach to identify inhibitors of this cysteine protease, and identified inhibitors of T. brucei. To discover inhibitors active(More)
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