**From:** Jérôme Hénin (*jerome.henin_at_ibpc.fr*)

**Date:** Thu Aug 26 2021 - 07:01:19 CDT

**Next message:**René Hafner TUK: "Re: eABF 3D sampling using distance Colvars + X and Y: averaged PMF difference to 1D sampling"**Previous message:**Chris Chipot: "Re: Unrealistically High Keq in eABF Seperation"**In reply to:**René Hafner TUK: "Re: eABF 3D sampling using distance Colvars + X and Y: averaged PMF difference to 1D sampling"**Next in thread:**René Hafner TUK: "Re: eABF 3D sampling using distance Colvars + X and Y: averaged PMF difference to 1D sampling"**Reply:**René Hafner TUK: "Re: eABF 3D sampling using distance Colvars + X and Y: averaged PMF difference to 1D sampling"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

Hi René,

*> What is the correct way to sample non-independent variables with proper guesses?
*

I'm not sure I can add much to answer this question. What you did seems correct, as far as I can tell.

The one concern I have is how you extract the "marginal" free energy profiles from the 3D profile. That is not very clear to me. A correct way would be to compute the integral of the Boltzmann factor (exp(-A(x,y,z)/RT)) over coordinates x and y.

Best,

Jérôme

----- On Aug 14, 2021, at 7:28 PM, René Hafner TUK <hamburge_at_physik.uni-kl.de> wrote:

*> Hi Giacomo,
*

*> yes I can confirm from the writings in the logfile stating:
*

*> "Enabling the extended Lagrangian term for colvar .. " for every colvar.
*

*> I make use of the CZAR estimator.
*

*> By the way: I am using NAMD 2.14.
*

*> René
*

*> On 8/14/2021 7:17 PM, Giacomo Fiorin wrote:
*

*>> Hello René, can you confirm that you are using extended ABF, and more
*

*>> specifically what estimator you used? (CZAR or Zheng/Yang).
*

*>> Orthogonality between variables is only required for straight ABF, where the
*

*>> force on the variable is obtained by projecting the atomic total forces
*

*>> directly, rather than using the extended-mass trick.
*

*>> Giacomo
*

*>> On Sat, Aug 14, 2021 at 11:24 AM René Hafner TUK < [
*

*>> mailto:hamburge_at_physik.uni-kl.de | hamburge_at_physik.uni-kl.de ] > wrote:
*

*>>> Hi,
*

*>>> I am trying to use a distance like colvar to sample a surface with a ligand
*

*>>> using extended ABF.
*

*>>> In order to speed up the surface sampling process I turned the abf line into a
*

*>>> 3D one where I also sample the X and Y direction.
*

*>>> My colvar file roughly looks like:
*

*>>>> colvar { name X; distanceZ ... } # Ligand distance from Membrane Center in X
*

*>>>> direction
*

*>>>> colvar { name Y; distanceZ ... } # Ligand distance from Membrane Center in Y
*

*>>>> direction
*

*>>>> colvar { name distanceFromMembrane} # Ligand local distance from Membrane
*

*>>>> Surface (selfdefined)
*

*>>>> abf { colvars X Y distanceFromMembrane; ... }
*

*>>> This means the third variable is not independent from/orthogonal to X and Y but
*

*>>> that shouldn't be and issue when using eABF.
*

*>>> Comparing 1D run and 3D run (averaged the 3D PMF over X,Y to get
*

*>>> PMF(distMembrane) )
*

*>>> * When I did 1D sampling ( only distanceFromMembrane) I obtained rougly
*

*>>> 5.5kcal/mol as dG (difference from Minimum to a point far away from Membrane)
*

*>>> * When I do 3D sampling using "subtractAppliedForce on " in all 3 colvars I
*

*>>> obtained dG ~ 4kcal/mol. (I used the term "subtractAppliedForce" because I
*

*>>> initially used metadynamics +eABF)
*

*>>> * When I do 3D sampling using "subtractAppliedForce off " in all 3 colvars I
*

*>>> obtained dG ~ 1-2kcal/mol.
*

*>>> What is the correct way to sample non-independent variables with proper guesses?
*

*>>> (I expect the 3D to reconstruct the 1D sampling case when done correctly and
*

*>>> just help improving the sampling of the whole surface)
*

*>>> Kind regards
*

*>>> René
*

*>>> --
*

*>>> --
*

*>>> Dipl.-Phys. René Hafner
*

*>>> TU Kaiserslautern
*

*>>> Germany
*

*> --
*

*> --
*

*> Dipl.-Phys. René Hafner
*

*> TU Kaiserslautern
*

*> Germany
*

**Next message:**René Hafner TUK: "Re: eABF 3D sampling using distance Colvars + X and Y: averaged PMF difference to 1D sampling"**Previous message:**Chris Chipot: "Re: Unrealistically High Keq in eABF Seperation"**In reply to:**René Hafner TUK: "Re: eABF 3D sampling using distance Colvars + X and Y: averaged PMF difference to 1D sampling"**Next in thread:**René Hafner TUK: "Re: eABF 3D sampling using distance Colvars + X and Y: averaged PMF difference to 1D sampling"**Reply:**René Hafner TUK: "Re: eABF 3D sampling using distance Colvars + X and Y: averaged PMF difference to 1D sampling"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

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