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As far as I recall, it shouldn't matter, although if you have interleague on, it might mess with things. Note, however, OOTP only cares that the league structure specified in the header of the schedule file matches the league structure set up in the game. It does not actually care what league structure the schedule of games itself is set up for.
In other words, you could, for example, have a league set up as having no interleague play and yet use a schedule that contains interleague play. As long as you change the interleague setting in the header of the schedule file to be no, OOTP should use the schedule properly.
I haven't actually tested it, but the same concept of 'tricking' the game should work for league structure as well.
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