[gmx-users] seeming paradox with gmx wham
nedomacho at gmail.com
Mon Mar 12 00:37:41 CET 2018
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?
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