Open source software shouldn't be a problem. Pretty much anything that has been ported to 64-bit big-endian also works on s390x. The architecture is otherwise pretty non-challenging: always 4K pages, strong memory model. Pre-built binaries are a different matter, of course.
The problem with access is not access as such, but the fact that the community hardware that you can access for free tends to be heavily oversubscribed (or maybe connected to a mismatched storage system).
I've never used a mainframe, but I did manage to introduce a small performance regression in gcc that someone complained about (I did fix it, yes). ;-)
Turned out that s390 couldn't fuse cmp+jmp when the operand was a 8-bit value (_Bool). (That was a while ago, maybe current generation mainframe HW can do it?)
The problem with access is not access as such, but the fact that the community hardware that you can access for free tends to be heavily oversubscribed (or maybe connected to a mismatched storage system).