The key really to me is the strat, for the real cutting through tone. if you use humbucker guitar, adjust your tone settings for a bit brighter sound. I'd try to not over do the gain, push more with the power amp sims and like rickboot said plexi sims would be good i'd bet.
IMHO, Frusciante isn't about the tone of the amp, it's more his style of playing that makes his tone, real percussive, with lots of ghost strums, and muting with syncopation is probably more important for his tone than the amp settings themselves. This is not the case for me with other guitarists, like Slash, Gilmour, EVH, etc. They are a combo of techniques and the settings. For me Frusciante is more the feel than anything else.