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Updated: Mar 29, 2026

Covalent Attachment of Single Molecules for AFM-based Force Spectroscopy
Published on: March 16, 2020
Revisiting the Exact Relation between Potential of Mean Force and Free-Energy Profile
1Multi Scale Mechanics, Faculty of Engineering Technology, and Computational BioPhysics, Faculty of Science and Technology, and MESA+ Institute for Nanotechnology, University of Twente , P.O. Box 217, 7500 AE Enschede, The Netherlands.
Abstract:
Constraints are convenient in the calculation of free energy profiles via molecular dynamics simulations, but they subtly alter the phase space distribution. In a recent letter of a related title in this journal, Wong and York [J. Chem. Theory Comput. 2012, 8, 3998-4003] suggest replacing Fixman's mass-metric correction with its inverse and adding a Jacobian contribution to the potential of mean constraint force. This letter refutes both suggestions, discusses the underlying interpretation problems, and provides supporting numerical simulations.
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