It can be done.. your problem is going to be stuttering in the game any time it needs to pull any information off of the drive.
The interface of the external drive is much slower than the internal interface.
If you absolutely must keep it off the wife's hard drive, you might try putting AH and RAM-drive software onto a "pen drive"... then you can create a RAM-drive (this is assume she has more than enough system RAM available), copy AH onto that and run it from there.
Just an idea though.