Repro steps:
1. Open the attached file "OneProtein.sky"
2. Wait a few seconds until protein metadata has finished updating.
3. File > Save (or Save As)
Result:
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Skyline
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Failed writing to E:\OneProtein.sky.

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OK More Info
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System.Reflection.TargetInvocationException ---> pwiz.Skyline.Util.AssumptionException
   at pwiz.Skyline.Util.Assume.Fail(String error) in C:\proj\skyline_22_2\pwiz_tools\Skyline\Util\Util.cs:line 2080
   at pwiz.Skyline.Model.Serialization.DocumentWriter.WritePeptideGroupXml(XmlWriter writer, PeptideGroupDocNode node) in C:\proj\skyline_22_2\pwiz_tools\Skyline\Model\Serialization\DocumentWriter.cs:line 154
   at pwiz.Skyline.Model.Serialization.DocumentWriter.WriteXml(XmlWriter writer) in C:\proj\skyline_22_2\pwiz_tools\Skyline\Model\Serialization\DocumentWriter.cs:line 71
   at pwiz.Skyline.Model.SrmDocument.Serialize(XmlTextWriter writer, String displayName, SkylineVersion skylineVersion, IProgressMonitor progressMonitor) in C:\proj\skyline_22_2\pwiz_tools\Skyline\Model\SrmDocument.cs:line 2263
   at pwiz.Skyline.Model.SrmDocument.SerializeToFile(String tempName, String displayName, SkylineVersion skylineVersion, IProgressMonitor progressMonitor) in C:\proj\skyline_22_2\pwiz_tools\Skyline\Model\SrmDocument.cs:line 2238
   at pwiz.Skyline.SkylineWindow.<>c__DisplayClass753_1.<SaveDocument>b__0(IProgressMonitor progressMonitor) in C:\proj\skyline_22_2\pwiz_tools\Skyline\SkylineFiles.cs:line 1011
   at pwiz.Skyline.Controls.LongWaitDlg.RunWork(Action`1 performWork) in C:\proj\skyline_22_2\pwiz_tools\Skyline\Controls\LongWaitDlg.cs:line 254
   --- End of inner exception stack trace ---
   at pwiz.Skyline.Util.Helpers.WrapAndThrowException(Exception x) in C:\proj\skyline_22_2\pwiz_tools\Skyline\Util\Util.cs:line 1965
   at pwiz.Skyline.Controls.LongWaitDlg.PerformWork(Control parent, Int32 delayMillis, Action`1 performWork) in C:\proj\skyline_22_2\pwiz_tools\Skyline\Controls\LongWaitDlg.cs:line 202
   at pwiz.Skyline.Controls.LongWaitDlg.PerformWork(Control parent, Int32 delayMillis, Action`1 performWork) in C:\proj\skyline_22_2\pwiz_tools\Skyline\Controls\LongWaitDlg.cs:line 140
   at pwiz.Skyline.SkylineWindow.SaveDocument(String fileName, Boolean includingCacheFile) in C:\proj\skyline_22_2\pwiz_tools\Skyline\SkylineFiles.cs:line 1018
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Fixed by https://github.com/ProteoWizard/pwiz/pull/2443