If you're looking to hold your ProSeries data [only] on a portable drive it can be done, but it is not recommended.  The data would be secure but each computer has it's own HomeBase and you'll be screwing that up as well as the E-File HomeBase transferring the portable drive back and forth.

Either keep all your data on one computer, and remote login or do the backup and restore feature.

But I would only e-file from one machine.  It makes life a lot easier.  Not required but recommended.