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Best way to travel from Germany to Prague?

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We are traveling through southern Germany (Rhine, Mosel, Romantic Road and surrounds) with another couple in late September through mid-October. W plan to drive in Germany but have heard we shouldn't try to drive from Germany to Prague. We would like to several days in Prague. What is the best travel method between Germany and Prague? W initially planned to take the train from Munich to Prague and back. We have been told by a contact in Germany that is not a good choice. I would love to hear from other travelers who have spent time in both places and get your recommendations. Thanks!

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