A hard drive's transfer rate will depend on how fast it spins (5400 rpm, 7200 rpm, etc) along with how many sectors there are per track. Assuming you are not doing any massively intense I/O, you should be able to run Linux off a USB drive just fine.
However, if you really want to be able to run Linux from USB, then your PC must support booting from a USB device. Go into BIOS, and look at the choices in the boot sequence menu. Unless you see USB listed as an option, practically speaking you are out of luck. Good luck with it either way
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