  Free energy is arguably the most importance function(al) for understanding of
molecular systems. A number of rigorous and approximate free energy
calculation/estimation methods have been developed over many decades. One
important issue, the continuity of an interested macrostate (or path) in
configurational space, has not been well articulated, however. As a matter of
fact, some important special cases have been intensively discussed. In this
perspective, I discuss the relevance of configurational space continuity in
development of more efficient and reliable next generation free energy
methodologies.
