Trail and error is a deal for very rich people. When you do not know, you do not do it if you do not was to do it again. First, I have found that no one every wants to go slower. They have never ever called me back to ask me if I can make it go slower, its always pushing it to the extrem-er! I did an engine 2 years ago and done all the math with everything I have learned in 40 years of engine building and told him to keep this engine at a 300 hp shot of NOS with my tune up only. He ran the engine for about 3 months and finally go beat. So he calls me and ask me if we could put 400 on the engine. I said sure but when it breaks it will break badly. I gave him my best tune up and hoped the head gaskets, pins, rings and tuner he used was dead on. It ran beautiful and once again he was on top. Now we have several months and guess what, he called me ask now asked me for a 500hp tune. I told him now its gonna be a margin of error area of a fraction figuring cylinder pressures, rpm, heat, fuel, dynamic workings of the whole engine to get from point a to b. I advised him with a big NO. He still wanted my tune. I gave it to him and said, "when it comes apart it will be ugly" Well he called me back that Monday and told me the little 434ci SBC Dart Block Billet Crank, forged Wiseco NOS pistons, tool steel pins and every thing else I shoved in this with EAGLE steel rods went 5.06 in the 1/8 and he won. Now he has his mind set nothing will break the engine. It did stay together and the point is never put it on the edge if you do not have to.
He has never pushed it any further because I know where I put it and I always leave room for growth. Men can never go fast enough. So my answer to you is that I would use 4:1 compression with a custom piston and your tune up will be so safe you will have plenty of time for growth. A little extra spent right now on custom pistons for your application will allow you to run 30 PSI of boost with pump gas if you want to. We have done this a few times and people always do the same thing, they call and say wow!. Now, you do have to build the bottom end, with rings, connecting rods, crankshaft to handle the power, or it will just break. So if your engine parts are marginal, you can still run the 4 or 5:1 or even 6:1 compression and be as safe as you want with 15-20lbs of boost and your margin of error can be tuned by Ray Charles. It will not be as sensitive to extreme pressures which allow you to be a yard stick off and it will not hurt it. Just read your spark plugs and use common sense. I have found E85 requires no inter cooling needed at all and it is readily available at the pump in most places. Your engine will stay super cool with minimal cooling items, no special fans, nothing but a water pump, stock fan shroud, fan and a good set of belts. I would tell you something but I think people will not understand the principal so if you want to private message me I might hint it to you if you would like, hope this helps a little