What exactly do you mean by "not responding"? Are you saying that Task Manager says that Skyline is "Not Responding"?
Can you send us a screenshot of what the Skyline window looks like when it is in this state?
If Task Manager does not say that Skyline is "Not Responding" but clicking on anything in Skyline does not do anything, the problem might be that Skyline is trying to show a message box, but, for some reason, the message box appeared behind the Skyline window instead of in front of it. We have had a few bugs like that. I am not sure exactly what you can do to be able to see the message box if you are in that state. You might be able to press the Windows key and the letter "D" at the same time, which will minimize all of the windows on the screen. Sometimes after you do that you might be able see the message box that was hidden before.
It might be helpful if you could send us your Skyline document.
In Skyline you can use the menu item:
File > Share
to create a .zip file containing your Skyline document and supporting files including extracted chromatograms.
Files which are less than than 50MB can be attached to this support request. You can always upload larger files here:
https://skyline.ms/files.url
If Skyline is really stuck, you might not be able to use the "File > Share" menu item, and it's also possible that seeing your Skyline document might not be sufficient for us to figure out what is going wrong.
You might have to also send us all of your peptide search result files and mzML files.
You could package everything up into a zip file and upload it to that same spot:
https://skyline.ms/files.url
-- Nick