I am seeing the exact same issue, except with a Kindle 3. I maintain my Calibre library on a NAS device, and an earlier thread mentioned that the 'on device' field for each e-book was updated each time the Kindle was attached or an e-book transferred. It seems the network overhead may cause the 'Not Responding' issue as Calibre is updating each e-book.
Does any of this match your configuration?
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