The reaction coordinate definition doesn't matter as long as it is not a periodic coordinate. If it is a periodic coordinate, it must be in degrees. The biasing potential must be a harmonic function of the form k*(x-x0)^2, where x is the reaction coordinate (however it is defined). It's not clear what you mean by "free energy values roughly 10 times higher than expected". The free energies are defined only to within a constant (you can shift the entire surface up or down by an arbitrary constant). It is only differences in free energies that have any meaning. If you have a small example (1 mb or less) that exhibits an issue, feel free to email it to me off-list and I can help you out. -Tim
________________________________
From: Ameni BEN ABDELJAOUED via AMBER <amber.ambermd.org>
Sent: Thursday, May 1, 2025 12:16 PM
To: amber.ambermd.org <amber.ambermd.org>
Subject: [AMBER] Does mbar in fe-toolkit support linear conbination distance as a CV when reconstructing FES from US?
Hi everyone,
I’ve been using MBAR from the fe-toolkit package to reconstruct a 1D PMF, aiming to validate an issue I encountered with my input when analyzing a reaction free energy profile from a QM/MM umbrella sampling simulation reconstructed with WHAM.
The collective variable (CV) I used is a linear combination of two distances with different weights — an antisymmetrical distance (ASD) with weights scaled as 2 and -1, to reflect a two-step reaction mechanism.
According to the MBAR documentation, the force constant unit should be kcal/mol·(unit)². I therefore kept the same biasing constant as I used in WHAM (1/2, corresponding to the Amber disang file). However, I was surprised to see that MBAR produced free energy values roughly 10 times higher than expected — both in terms of expected values and compared to WHAM (grossfield) results.
When I rescaled the force constant by a factor of 1/5, the results became much more plausible. This makes me wonder: is MBAR particularly sensitive to the exact definition or scaling of the CV? More specifically, does MBAR inherently not support antisymmetrical distances, or is there a recommended way to treat such CVs?
I’d greatly appreciate any insight or references where I could learn more about these behaviors.
Thank you in advance!
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Received on Thu May 01 2025 - 10:30:04 PDT
