Question
What exactly do the Simulation Profiles settings do?

Answer
Simulation Profiles:
The CMYK Simulation Profile print option allows you to print press proofs or simulations. This setting specifies the offset press standard or other color printing device that you want to simulate.

The CMYK Simulation Profile setting you specify depends on the press standard for which the CMYK data was separated.

For images that were separated using a custom separation (such as a separation produced with an ICC profile), choose the corresponding profile on the Fiery with the CMYK Simulation Profile setting.

For images that were separated for SWOP, choose SWOP as the CMYK Simulation Profile setting.

Two settings are available if you want no CMYK simulation:

The None setting sends your original CMYK data to the copier with calibration applied, but without conversions to simulate another printer.
The None setting is recommended if you use another
color management system instead of ColorWise (for example, ColorSync or Photoshop). In this case, the Fiery is expecting to receive CMYK data already in the device color space of the Fiery PRO80. The Fiery PRO80 will not convert the data, but it will apply calibration.

The ColorWise Off setting sends your original CMYK data to the copier without calibration applied and without conversions to simulate another printer. The CMYK data is still subject to maximum density constraints, however.
The ColorWise Off setting is not available in Color Setup and cannot be the default CMYK Simulation Profile setting. You choose this setting for a specific job.