[gmx-users] seeming paradox with gmx wham

[Alex]

Just to add to my question... The pull code for the umbrella sampling from each of the N configs, as used in Justin's tutorial, is

pull_coord1_type        = umbrella
pull_coord1_geometry    = distance
...
pull_coord1_dim         = N N Y

So, in each of the generated pullf and pullx files we sample a flat slice at a given Z, and the reported forces and displacements are along Z. What appears to be the reaction coordinate in our case is the radius from the pore mouth, and one has to sample a set of hemispheres from a series of radius values. Is this at all a possibility?

Alex


On 3/11/2018 5:37 PM, Alex wrote:
> Hi all,
>
> I am looking at what appears to be a paradox. Consider the following 
> situation: we have a graphene membrane with a single pore of a 
> particular type. The pore is located at (x0, y0, h/2), where h is the 
> box height. The membrane is position-restrained along its perimeter 
> and immersed in a solution of NaCl. The pore is designed to trap 
> anions -- and it does, if you artificially bring an anion close enough 
> to the mouth of the pore and run the simulation at, say, room temp.
>
> However, the ions do not bind by themselves. 100s of nanoseconds of 
> simulations with high salt concentrations -- nothing. So, I expect a 
> high barrier associated with ion dehydration when entering the pore. 
> Following Justin's tutorial and generating a total of 30 1A-spaced 
> configs (15 below h/2, 15 above h/2) along (x0,y0), gmx wham yields a 
> 6.5 kJ/mol barrier, which isn't high at all! Just from the pullf data 
> when generating the configs (pull along Z with x and y restrained), 
> the naive integral of the pulling force prior to overcoming the 
> hydration barrier yields 4 kJ/mol -- consistent with the WHAM result. 
> But in reality, ions (which aren't restrained around (x0,y0) are not 
> observed to bind, which brings us to my question...
>
> It looks like when an ion approaches the pore parallel to the membrane 
> normal, the barrier is indeed low, while approach at an angle yields 
> higher barriers. It appears that WHAM produces the free energy curve 
> resulting from frequent sampling approach directions that have the 
> lowest possible barrier. Is it possible to modify this calculation to 
> give equal weight to all approach directions?
>
> Thank you,
>
> Alex
>
>