I find the best shred lead sound comes by having gain up 3/4 to full (depending on your gear) and everything else between 12 and 2 o'clock (tweaked to suit your set up). This basic setup works especially well for me on an Ibanez Jem and a Marshall amp. Some of the guys here may complain about overuse of the neck pickups, but the fact is a lot of shredders use them especialy with sweep picking. You will get a much thicker sound from the neck but the bridge is best for legatto and tapping. Hope that helps