Transmembrane signaling mechanisms of plexin - Supplement

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This application is to request fund for purchasing of a high-end computation and data storage system for the cryo-electron microscopic (cryo-EM) work under the parent project that is focused on cryo-EM structural and mechanistic analyses of the transmembrane receptor plexin. In the past few years, the parent project has generated a number of high-impact cryo-EM structures of plexin and related transmembrane receptors, which substantially advanced the understanding of their signaling mechanisms. During this period, the infrastructure for computation and data storage have become a major bottleneck. The throughput of cryo-EM data collection has been increasing at a very fast rate, leading to vast amounts of data that enable the determination of high-resolution structures of proteins that was previously not possible. Accordingly, fast computers are required for processing these data and take advantage of new methods that are improving on a daily basis but also more resource demanding. Large storage servers are needed for secure storage and easy access of the data. The lab has been relying on a single workstation with a 12-TB hard-disk. With the data collection rate at ~2 TB per day and ~5 TB per trial of a protein, the available disk space is severely limiting the progress of the project. The calculation of each structure on the GPU workstation takes days or weeks for difficult cases, which leads to delays as datasets waiting in the queue. In addition, the current GPUs have 12 GB memory, limiting the size of the protein complex structures that could be processed. This proposal therefore requests for fund to purchase a computational system built for cryo-EM, with 16 GPUs with 48 GB memory and 1 PB RAID hard-disk unit. This is an invest that will greatly benefit the parent project and the research field for years to come.