Skyline does not normally try to find the .raw files when you open a document. Can you attach a screenshot of the error message you are seeing?

If you open a Skyline document, and Skyline tells you that it cannot find the raw data, that is probably because there is something wrong with the .skyd file. The .skyd file contains extracted chromatograms, and the .sky file contains peptide lists, peak areas, etc. The .sky file says which raw files are supposed to be in it, and, if Skyline does not see chromatograms from those files inside of the .skyd file, then Skyline will tell you that it cannot find the .raw files.

Normally, after chromatograms have been extracted, you no longer need access to the .raw files. The only exceptions are:
1. Clicking on a chromatogram to look at a particular spectrum
2. Edit > Manage Results > Reimport
3. You delete your .skyd file
In these cases, Skyline first tries to look for the .raw file in its original location, but, if Skyline does not find the .raw file there, Skyline will also look in the same directory as the .sky file.

Anyway, it sounds like you probably only copied the .sky file and did not get the .skyd file that goes along with it. If you want to move a Skyline document between computers, you should use the menu item:
File > Share > (complete)
to create a .zip file containing the Skyline document (.sky file) extracted chromatograms (.skyd file) as well as all other supporting files (.blib files, etc).

I do not believe that Skyline (or rather, ProteoWizard) knows how to read anything from .zip files. It sounds like you might want to try using filesystem compression, which causes the files to use less space on disk, but they look like regular files to everyone else. Here's a page that talks about how to do that on Windows:
https://www.howtogeek.com/133264/how-to-use-ntfs-compression-and-when-you-might-want-to/
There are similar things that you can do on Linux.

Dear Nick,

Sorry for the very late reply, I have been out of the lab for a while. But here I am back again analying data with Skyline!
Thank you very much for your answer!
In attachment is a schreenshot of the error message I see, I do not really understand if this is a .skyd file problem...could you give some more insights? Thanks a lot!

Ok, I think I got it: I was trying to click on the chromatogramm curve to look at the partcular MS2 spectrum (exception nr.1 in your answer)...
I did not realize this before,

Thanks again!

Best,
Ilaria Affolter

I know this is a very old post, but I wanted to ask about the "exception 1" that Nick mentioned. I am trying to do that exact thing - look at the spectra after importing files and extracting chromatograms. My problem is that our IT department remapped our network drives in the time since I imported the files, and so the file paths have changed from "Z:\ClientData..." to "X:\ClientData..." and Skyline cannot find the files using the "Z:\" path. I know that I could remap the drive back to "Z:\" so that Skyline would have the correct path again, but of course that will create havoc in all the other connections to the drive in other programs/documents/etc that are using the new server name. Reimporting files would also be a big headache, as I have >120 .raw files in this document. Is there a way to simply update the file path in Skyline, like in ProteomeDiscoverer where a user can update a file location? I have tried to do so in the Document viewer, but File Path field is grayed out as a non-editable field.

Thanks,
Josh