Re: Binding free energy tutorial

From: Nassar, Omneya (omnassar_at_UTMB.EDU)
Date: Wed Nov 07 2018 - 08:56:56 CST

Hi Jing,

Did you use “runFEP” or “runFEPmin”? You should use runFEPmin if you are using numMinSteps. Let me know if that fixes the problem.

Cheers,
Omneya

________________________________
From: owner-namd-l_at_ks.uiuc.edu on behalf of jing liang <jingliang2015_at_gmail.com>
Sent: Wednesday, November 7, 2018 08:22
To: dhardy_at_ks.uiuc.edu
Cc: Giacomo Fiorin; namd-l_at_ks.uiuc.edu
Subject: Re: namd-l: Binding free energy tutorial

WARNING: This email originated from outside of UTMB's email system. Do not click links or open attachments unless you recognize the sender and know the content is safe.

Hi,

I downloaded the binding free energy tutorial and it seems there have been some changes to the files
for instance a parameter numMinSteps which was not there some weeks ago (maybe I am wrong).
When I run the namd scripts for forward and backward systems it throws the following error using
different versions (2.12b and 2.13b):

ERROR: 'alchLambda' is a required configuration option
ERROR: when 'alch' is set
ERROR: alchLambda defines: Coupling parameter value
ERROR: The following variables were set in the
ERROR: configuration file but are NOT VALID
ERROR: runFEPmin

El mié., 31 oct. 2018 a las 10:31, jing liang (<jingliang2015_at_gmail.com<mailto:jingliang2015_at_gmail.com>>) escribió:
Hi everyone,

I ran the binding free energy tutorial case (alchemical route) with the suggested modifications. For the unbound simulation
I got the BAR estimator of -54.12 and for the bound case this estimator was -36.41. That BAR estimator was obtained through
the parseFEP plugin from VMD. By looking at the summary.png plot from parseFEP, I noticed that the forward and backward
pathways (in both bound and unbound cases) show a larger hysteresis (~10kcal/mol difference) than the one you presented
in the Fig. 5 of the tutorial. I got some questions, any comment is appreciated:

* Are all energy restraints included in the BAR estimator? I mean, for instance the free energy contribution due to the restraining
potential as in Fig. 7 of the tutorial. Or should I get the energy contribution by integrating some extra terms?

* In the tutorial it says that one can do "grep dA/DLambda rest-01.log" to get the restraints contributions, but I couldn't find that
output file.

* Should the binding free energy difference be equal to the (BAR estimator unbound) - (BAR estimator bound)?

Thanks.

El dom., 28 oct. 2018 a las 17:47, David Hardy (<dhardy_at_ks.uiuc.edu<mailto:dhardy_at_ks.uiuc.edu>>) escribió:
Hi Giacomo,

Thanks for clarifying. Sorry for my misunderstanding about how Colvars was now handling this configuration.

I will get in touch off-list with the tutorial authors.

Best regards,
Dave

On Oct 28, 2018, at 11:20 PM, Giacomo Fiorin <giacomo.fiorin_at_gmail.com<mailto:giacomo.fiorin_at_gmail.com>> wrote:

Hi everyone, I can confirm that the message:
colvars: Error: lower wall and upper wall are equal in the domain of the variable "Psi".
is obtained correctly, because -180° and 180° are the same angle. In much older versions, the Colvars walls code was simpler and it was possible to resolve the error internally by disabling the walls.

The improved version does not allow this as easily, and most importantly we agreed during earlier private conversations that an error message is more appropriate than a warning about incorrect input. The tutorial's input is wrong most likely due to inadvertently pasting the input for a Psi interval shorter than -180°:180°: this is a type of mistake that we all do often, but it is easy to fix by disabling the walls.

Jing, please disable the wall potentials for that example, and that will resolve your error. For more information about the very few example of syntax changes, this is the relevant section:
https://colvars.github.io/colvars-refman-namd/colvars-refman-namd.html#sec:colvars_config_changesta=02%7C01%7Comnassar%40UTMB.EDU%7Cac9464226c584941b1ce08d644bc7351%7C7bef256d85db4526a72d31aea2546852%7C0%7C0%7C636771973529322000&sdata=QH1xvLuhuqclkn8c2lK8hLR5RUU1yQxQkwP%2BVg56SIw%3D&reserved=0>

Giacomo

On Sat, Oct 27, 2018 at 4:35 PM David Hardy <dhardy_at_ks.uiuc.edu<mailto:dhardy_at_ks.uiuc.edu>> wrote:
Let's please keep our replies on the list.

I thought that Giacomo and Jerome had updated Colvars to still maintain backwards compatibility with the tutorial's older syntax for defining a harmonic collective variable, but maybe I'm mistaken. (Hey, if either of you see this, maybe respond?)

At any rate, the issue is then not a bug in the code (it seems to be giving a correct error message) but instead a bug in the tutorial. For now, you can solve this one yourself by taking a look at the Colvars chapter in the NAMD user guide to find out how to correctly define a "harmonicwalls" collective variable and then fixing the config file.

You'd be doing everyone involved a favor if you reply to namd-l with the fixed syntax.

Thanks.

--
David J. Hardy, Ph.D.
Beckman Institute
University of Illinois at Urbana-Champaign
405 N. Mathews Ave., Urbana, IL 61801
dhardy_at_ks.uiuc.edu<mailto:dhardy_at_ks.uiuc.edu>, http://www.ks.uiuc.edu/~dhardy/=siY7wQzBIVjrNPskKOURSwXbAlk4mm1cqBElvbFJHCE%3D&reserved=0>
On Oct 28, 2018, at 3:35 AM, jing liang <jingliang2015_at_gmail.com<mailto:jingliang2015_at_gmail.com>> wrote:
Hi,
thanks for your comments. I downloaded the 2.13b2 KNL version from ks.uiuc.edu<https://na01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fks.uiuc.edu%2F&data=02%7C01%7Comnassar%40UTMB.EDU%7Cac9464226c584941b1ce08d644bc7351%7C7bef256d85db4526a72d31aea2546852%7C0%7C0%7C636771973529332005&sdata=TUUecr98oTYZd5%2BPwaCLhW5TZRDNUkRoZVISQzSU6yw%3D&reserved=0> website. It doesn't show the
message I wrote before. Instead it says that the lower and upper wall values are the same for the angles:
 colvars:   Initializing a new "harmonicwalls" instance.
colvars:   # name = "Psiw"
colvars:   # colvars = { Psi }
colvars:   # outputEnergy = off [default]
colvars:   # timeStepFactor = 1
colvars:   # writeTISamples = off [default]
colvars:   # writeTIPMF = off [default]
colvars:   # forceConstant = 1 [default]
colvars:   # targetForceConstant = -1 [default]
colvars:   # lowerWalls = { -180 }
colvars:   # upperWalls = { 180 }
colvars:   # lowerWallConstant = 0.5
colvars:   # upperWallConstant = 0.5
colvars: Error: lower wall and upper wall are equal in the domain of the variable "Psi".
FATAL ERROR: Error in the collective variables module: exiting.
I don't get that error message if I use instead of -180 the value of -179.999 but I guess that could be a bug from
the code which might have other consequences?
Thank you.
El sáb., 27 oct. 2018 a las 10:15, David Hardy (<dhardy_at_ks.uiuc.edu<mailto:dhardy_at_ks.uiuc.edu>>) escribió:
Dear Jing Liang,
Please try running that part of the tutorial again with the most recent NAMD 2.13b2.  The "misunderstanding" between the tutorial configuration file and the Colvars module has recently been fixed.
Best regards,
Dave
--
David J. Hardy, Ph.D.
Beckman Institute
University of Illinois at Urbana-Champaign
405 N. Mathews Ave., Urbana, IL 61801
dhardy_at_ks.uiuc.edu<mailto:dhardy_at_ks.uiuc.edu>, http://www.ks.uiuc.edu/~dhardy/=XJ8ILKvFEZkdN59wBDRVFKyPbb7GuVEH4%2F7rEIHetDY%3D&reserved=0>
On Oct 27, 2018, at 3:37 AM, jing liang <jingliang2015_at_gmail.com<mailto:jingliang2015_at_gmail.com>> wrote:
Hi,
I downloaded the tutorial "Protein:ligand Standard Binding Free Energies: A Tutorial for Alchemical and Geometrical Transformations" in the site: https://www.ks.uiuc.edu/Training/Tutorials/%7C636771973529342009&sdata=QNnVQ2ofzgBBFzo%2F4CSxCOm9M0f2gCT5x6gNk11gh5A%3D&reserved=0>
The Alchemical Bound state simulation only ran fine for the backwards direction. In the forwards
direction it showed the following error: jacobi too many iterations.  I am working with the
version 2.12 shared memory version. Have you experienced this issue in the present test case?
Thanks.
--
Giacomo Fiorin
Associate Professor of Research, Temple University, Philadelphia, PA
Contractor, National Institutes of Health, Bethesda, MD
http://goo.gl/Q3TBQUipc2ZRs1mAmRoB6gXJjWl0%3D&reserved=0>
https://github.com/giacomofiorina=EQhRwCT3eJYuWSPL25TrKBjCPov7Apztqb0BxxxlHZA%3D&reserved=0>

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