Do you play it in open E? Like Little Martha? Try it sometime. Duane was big on open E.
Little Martha, yes; Melissa, no. I play lead, and learned all the pretty licks of Melissa in standard tuning. While it's possible in theory for me to re-learn them in open-E tuning, it's arguably not worth the effort.
But that said, I generally have a few guitars with me in a gig situation, the Strat and Les Paul in standard and the SG in open-E for slide and songs like Little Martha, so I don't have to re-tune on the fly.
So now you've given me a challenge. :-)