This bug has been there forever. However, I searched and didn't see it listed.

In a puzzle with a guide (and probably in electron density puzzles too), saving the puzzle, then restoring frequently causes the guide to move in relation to the protein. Something is happening to the origin of either the guide or the protein on a save or restore. This may be related to the "Align Guide" button.

This causes huge problems in "Quest to the Native" puzzles as frequently you create one band for each sidechain banding to the guide. If you save the puzzle and come back to it, all of your bands are useless since the guide has moved. The only solution is to delete all your bands and start over, losing many hours of work.