Re: Query regarding ABF Tutorial on Methane Hydration

From: Chris Chipot (chipot_at_ks.uiuc.edu)
Date: Tue Jun 22 2010 - 15:18:10 CDT

Dear Navendu,

> This is reagrding ABF-Tutorial on 'Calculation of hydration free energy
> of Methane'.
> I am trying to reproduce the PMF plot in the analysis section but have
> not been able to do so.
> Relevant files used in this work have been attached.
> Steps as mentioned in the tutorial were followed and here is a brief
> description of my implementation:
>
> 1. Generated a .psf file from the provided .pdb and topology files.
> 2. Solvated the system (15 A on all sides)
> 3. PBC set to 30. 30. 60. to generate vacuum in the z-direction.
> 4. Minimized and heated the system to 300 K. Equilibrated for 1.0 ns
> 5. Performed ABF calculations using the parameters as provided in the
> abf.conf file (reaction coordinate was split into 5 windows)
> 6. Created the plot by extracting data from .pmf file
>
> Following is the list of issues/queries :
> 1. Free Energy profile averages around zero rather than dipping to
> -3.0 kcal/mol.

Starting from the gas phase, the free energy should decrease when
methane approaches the water-air interface. This is due to favorable
dispersion interactions. The free energy subsequently increases as
the solute penetrates deeper in the aqueous medium. This is the
cavitation free energy, or the reversible work incurred to perturb
the structure of the liquid and form a cavity capable of accommodating
the methane molecule. Eventually the free energy levels off as the
solute approaches the center of the water lamella. The free-energy
difference between the gas-phase and the water-phase plateaus is the
hydration free energy and should amount to about +2.4 kcal/mol with
the Charmm27 force field.

> 2. Visualization of the simulation trajectory in VMD shows,
> - water box flattens in the x-y direction (probably because
> 'wrapwater' command is turned off). Is this correct ? (Please refer to
> the attached .dcd file)

Keep in mind that the simulation should be run in the canonical
ensemble to maintain the gas-phase head space above and below
the water lamella. Starting from an equilibrated water box run
in the isobaric-isothermal ensemble, increasing the dimension
in the z-direction and turning to the canonical ensemble, you
should not see much shrinking in the x,y-plane.

> - Methane molecule does not follow a standard path in the
> z-direction (I thought that it would follow a 1-D path in the
> z-direction moving out from the water phase into the gas phase. Please
> correct me if I am wrong)

The average force is exerted along the z-direction. What does it
mean? It means that for each altitude of the solute in that
direction, an average is carried out over all positions of the
solute in the corresponding x,y-plane. In order of your ensemble
average to converge, methane should diffuse freely in that plane,
so that all important solute-solvent configurations are properly
sampled.

> 3. How important is it to break the simulation into separate windows ? I
> have performed the simulation using both methods ( full vs broken
> reaction pathway)

This question has been answered previously. See 01/24/2009 thread.

> Simulations were also performed with 'wrapwater' command set to 'on',
> but the resulting free energy profile was still incorrect compared to
> the Tutorial analysis.
> Kindly suggest if there is a basic flaw in my system set up or
> simulation that is resulting in this error ? Does this have something to
> do with Standard state correction ?

Cheers,

Chris Chipot

_______________________________________________________________________

Chris Chipot, Ph.D.
on leave from Nancy Université, CNRS
Theoretical and Computational Biophysics Group
Beckman Institute
University of Illinois at Urbana-Champaign
405 North Mathews Phone: (217) 244-5711
Urbana, Illinois 61801 Fax: (217) 244-6078

                             E-mail: chipot_at_ks.uiuc.edu
                                     Christophe.Chipot_at_edam.uhp-nancy.fr
                             Web: http://www.ks.uiuc.edu/~chipot
                                     http://www.edam.uhp-nancy.fr

The light shines in the darkness, and the darkness has not overcome it.

                                                               John 1:5.
_______________________________________________________________________

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