Hello. It is definitely possible to perform MS/MS at both low-resolution (in the linear ion trap) and high-resolution (in the orbitrap) on an LTQ-Orbitrap instrument. You need to add a mass in the MSn window for each scan event. I believe that it is also possible to give it an MS/MS list but that might be dependent on the version of Xcalibur. Attached is a PDF from Thermo's website on doing quantitative analyses on an LTQ-Orbitrap instrument. If you need more specific details on collecting your data you might want to contact Thermo for specifics.

Best of luck in your experiments and thanks for using Skyline.
Mike