Post some samples!! Do the MD421 IRs live up to your expectations? Pretty interesting mic. In my opinion it's shoddily built and wickedly over-priced, but if it sounds good that's all that matters, hahah. From my experience the presence 2 IRs are the "ideal" ones to be using. They have the presence knob on the 6505+ set to 8, which is where I always end up setting it when I run guitars through it for re-amping, etc. It seems the most balanced to me. The presence 3 IRs have the 6505+ presence knob set to nine, which is the highest I ever set the presence. Beyond that it becomes to fizzy for me. So I tend to avoid using pres_4 and pres_5 IRs, except maybe for rooms and special fx. I see a lot of people using the presence 4 or 5 IRs which is pretty extreme and potentially fizzy. If those IRs sound the best, you should probably turn the treble and presence on your amp head sim up and try to get it down to using a 1, 2 or 3 IR for best results. Obviously there are no rules and you can use what you want, but pres_2 IRs generally will best reflect the true balance of your amp head settings. Another tip is don't run a tube screamer plug before the TS impulses, or LePou's Legion plug-in (it has a built in TS I believe). However, you might want to try a tube screamer plug-in before using the non-TS impulses to tighten them up.