Configurational space continuity and free energy calculations

TL;DR

This paper discusses the importance of configurational space continuity in developing more efficient and reliable free energy calculation methods for molecular systems.

Contribution

It highlights the role of configurational space continuity in advancing free energy methodologies, addressing a previously underarticulated issue.

Findings

Emphasizes the significance of configurational space continuity in free energy calculations.

Connects configurational space properties to the development of improved methods.

Provides a perspective on future methodological improvements.

Abstract

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.