re: substitution - no. The substitution logic in the sim is flat-out terrible.
As for numbers on a penalty of bonus... can't say, really. I've never tested the penalty out. The bonus is relative to the type of defenses and tempos you face. The bonus will be higher in lower cap leagues where people can't stock up on as much defense. It seems that in the current $42m environment, getting 100 ast% (cumulative, 5 on floor) and up-tempo brings shooters to and maybe just above their RL averages. My testing is in extremely early phases, however, as the team I'm running this with just hit the all-star break and is in a division with a much better than average defensive team and several teams that are running slow-down on me. I've got a 125 ast% team that just started as well... results seem much better in it. jlg has several 150+ ast% teams either running or have run in the past... his results are way higher than what I've been getting. He's seeing guys with 15-20% increases (a 48% guy shooting 56%; a 60% guy shooting 72%).
So with all that in mind, nothing thus far is conclusive.