RE: PMF calculation

From: Mahdi Mousaei (mahdi.mousaei_at_ucalgary.ca)
Date: Thu Jul 11 2019 - 15:59:42 CDT

Hello,
Thanks for your reply. The provided information is great.
I have both the PME and cutting off in my conf file:

# PME (for full-system periodic electrostatics)
PME yes
PMEGridSpacing 1.0

# Force-Field Parameters
exclude scaled1-4
1-4scaling 1.0
cutoff 12.
switching on
switchdist 10.
pairlistdist 16

Thank you.

Best Wishes,
Mahdi

________________________________
From: Giacomo Fiorin <giacomo.fiorin_at_gmail.com>
Sent: Thursday, July 11, 2019 1:28:20 PM
To: NAMD list; Mahdi Mousaei
Cc: Souvik Sinha
Subject: Re: namd-l: PMF calculation

Hello Mahdi, overlapping windows are a necessary condition for a converged PMF, but are not a sufficient condition. You may very well have covered the entire region of interest, but if the windows are still equilibrating the distribution may be smooth, but not be the correct one (yet).

Any error estimate based entirely on the unbiasing method (WHAM, MBAR, etc) assumes that equilibrium sampling is valid over the entire simulation. There are some techniques, e.g. DHAM, to try to automatically remove non-equilibrium effects (as opposed to you manually truncating the trajectory) but they also assumes that equilibrium is reached before the end of each window's trajectory. As a corollary, you should take the error bars generated by those methods with the proverbial grain of salt.

Keep also in mind that the specifics of your system will generate electric fields that can be longer ranged than you think. After all, I presume you are not cutting off Coulomb forces at 12 Ň but are using Ewald or PME, right? Only a PMF computed across the entire unit cell should be periodic at the edges (in the absence of an applied voltage ramp).

Giacomo

On Thu, Jul 11, 2019 at 4:12 PM Mahdi Mousaei <mahdi.mousaei_at_ucalgary.ca<mailto:mahdi.mousaei_at_ucalgary.ca>> wrote:
Thank you for your reply. Thatís true, but if we the ion goes from the water and end in water, this could happen?

Best Wishes,
Mahdi

________________________________
From: Souvik Sinha <souvik.sinha893_at_gmail.com<mailto:souvik.sinha893_at_gmail.com>>
Sent: Thursday, July 11, 2019 1:08:08 PM
To: NAMD list; Mahdi Mousaei
Subject: Re: namd-l: PMF calculation

The entry and exit of the ion channel may have different residual distribution which may cause different interaction of the ion with the pore residues, thus the asymmetric PMF along the channel axis. Dose it make sense?

On Fri, 12 Jul 2019, 00:46 Mahdi Mousaei, <mahdi.mousaei_at_ucalgary.ca<mailto:mahdi.mousaei_at_ucalgary.ca>> wrote:
Hello to All,

I have used NAMD tutorial for PMF calculation of ion permeation through the ion channel. I have enough sampling due to the overlapping between the histograms. But, I see the asymmetric PMF profile which does not make sense ( I think) since the system is periodic and there is bulk water up and down of the system.
Does anyone have any suggestion why this is happening or any kind of analysis how I can find the reason?

Best Wishes,
Mahdi

--
Giacomo Fiorin
Associate Professor of Research, Temple University, Philadelphia, PA
Research collaborator, National Institutes of Health, Bethesda, MD
http://goo.gl/Q3TBQU
https://github.com/giacomofiorin

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