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<img src='content_image/343390.jpg'>

12) is more complex, the increased difficulty of implementation is no greater than using the Bennett Acceptance Ratio [4] relative to unidirectional estimates of free energy differences , and does not require sampling from more ensembles. Expected statistical efficiency gains should make this investment worthwhile. 

## ACKNOWLEDGMENTS 

D.M. thanks Artur Adib for sharing and explaining his manuscript, and Lee Makowski for sponsoring a Director’s Postdoctoral Fellowship. 

∗ Electronic Address: daveminh@gmail.com 

[1] A. Gelman and X.-L. Meng, Stat. Sci. 13 , 163 (1998). 

[2] C. Jarzynski, in Computational Methods for Macromolecules, Lecture Notes , edited by T. Schlick and H. H. Gan (Springer, Berlin, 2002), vol. 24. 

