Hey guys, I want to get John Frusciante's tone, especially like on The Zephyr Song. Only problem is I have a Les Paul and can't seem to make it sound near enough to it through my vypyr. I'd be grateful for any idea, thanks.
To get the Les Paul to do it I suppose you could get coil-split the pick-ups with a push-pull pot. That would get closer to the Strat tone.
'And after a while, you can work on points for style.
Like the club tie, and the firm handshake,
A certain look in the eye and an easy smile.'

'You have to be trusted by the people that you lie to,
So that when they turn their backs on you,
You'll get the chance to put the knife in.'
Yeah you'd probably want to get single coil tone from your guitar somehow, be it coil splitting or buying a guitar with single coils. As for the vypyr, try the brit and plexi on both green and red mode, they should get you in the Marshall ballpark.
without different pickups or some EQ tnal effects, i would find that its hard to get strats to soud like the famous people that use them because the gear they use is far beyond what most normal people use.

for example, gilmour, frischante etc all play through huge vintage amps that really give a different sound to a strat than say, playing through a hot rod.

i mean yeah i was reading a magazine interview where frischante said he A/Bs a marshal silver jubilee and a 200 watt vintage marshal.

THEN, he uses effects sparingly and for recording uses synth effects to change his tone instead of relying on individual pedals.

so thats going to be hard to emulate. in fact, with my setup, i prefer to copy famous strat players with humbuckers because people like gilmour has some a thick, creamy tone, i cant get it from strats use with my gear.
^ Maybe you are doing something VERY wrong.
Emulating singlecoil tones with humbuckers?
Really, WTF?