Re: Fwd: FEP protein-ligand tutorial 2017 unclear section

From: JC Gumbart (gumbart_at_physics.gatech.edu)
Date: Sat May 05 2018 - 07:20:13 CDT

How could ParseFEP deal with the restraints? Even the ghost ligand in Alchemy:Bound is still being held to the binding site. If you haven’t read the source paper yet https://www.ncbi.nlm.nih.gov/pubmed/23794960 <https://www.ncbi.nlm.nih.gov/pubmed/23794960> , it might help with the logic behind the different steps.

I don’t remember the exact format of the output, but I imagine grep + awk/sed will extract the relevant lines.

Best,
JC

> On May 5, 2018, at 2:43 AM, Francesco Pietra <chiendarret_at_gmail.com> wrote:
>
> Hi Giacomo:
>
> I believe to understand perfectly (and fully agree with) your point. May be that some of my words looked like unappropriated to developers, my contrary wish notwithstanding. I was just terrified by the amount of hand work to do.
>
> At any event, my point was (and is) whether those thermodynamic integrations have to be accounted for in calculating /\G from ParseFEP, or restraint of the ligand (free or bound to the protein) is already accounted for by ParseFEP dealing with Alchemy:Unbound and Alchemy:Bound calculations at the 2017 tutorial. I.e., whether the TI calculations at Restraints:Unbound and Restraints:Bound can be just skipped.
>
> It might be better that people with an experimental background, like me, leave theoretical approaches to theoreticians. However, the point is, that what I am trying to calculate does not find an experimental approach yet, while my interest is in the system.
>
> thanks for your understanding
>
> francesco
>
>
>
> On Sat, May 5, 2018 at 12:04 AM, Giacomo Fiorin <giacomo.fiorin_at_gmail.com <mailto:giacomo.fiorin_at_gmail.com>> wrote:
> I think you are going about this the wrong way.
>
> It's not that every broken or missing feature is a punishment: instead, good academic software is a gift to you. Please understand that.
>
> Giacomo
>
> On Fri, May 4, 2018 at 3:47 PM, Francesco Pietra <chiendarret_at_gmail.com <mailto:chiendarret_at_gmail.com>> wrote:
> It seems that the contribution to /\G of restraining the ligand is accounted for in the .namd files with both /Alchemy:Bound and /Alchemy:Unbound, and therefore with ParseFEP. Am I wrong?
>
> If I am wrong, is any script to extract /\G from the thermodynamic integration runs, so as to "add" to the ParseFEP output? Doing that manually, and necessarily repeatedly for long simulations is a punishment that perhaps I don't deserve.
>
> thanks
> francesco
>
> On Fri, May 4, 2018 at 5:43 PM, JC Gumbart <gumbart_at_physics.gatech.edu <mailto:gumbart_at_physics.gatech.edu>> wrote:
> The two files are forward and backward runs of what is essentially TI. It’s been a while since I’ve done it, but I believe you can extract dG/dlambda from the log files and then integrate it.
>
> Best,
> JC
>
>> On May 4, 2018, at 1:39 AM, Francesco Pietra <chiendarret_at_gmail.com <mailto:chiendarret_at_gmail.com>> wrote:
>>
>> Perhaps this question about "FEP protein-ligand tutorial 2017 unclear section" has passed unnoticed. Thanks for paying attention to.
>> fp
>> ---------- Forwarded message ----------
>> From: Francesco Pietra <chiendarret_at_gmail.com <mailto:chiendarret_at_gmail.com>>
>> Date: Wed, May 2, 2018 at 9:51 PM
>> Subject: FEP protein-ligand tutorial 2017 unclear section
>> To: NAMD <namd-l_at_ks.uiuc.edu <mailto:namd-l_at_ks.uiuc.edu>>
>>
>>
>> Hello:
>> With reference to the 2017 "Protein:ligand standard binding free energies: A tutorial for alchemical and geometrical transformations" by Gumbart, Roux, Chipot,it is not clear to me how to deal with the two sections of the archive files
>>
>> 1) Restraints:Bound
>> 2) Restraints:Unbound
>>
>> in the frame of files provided in
>>
>> 3) Alchemy:Bound
>> 4) Alchemy:Unbound
>>
>> i.e, how the contribution of restraints in 1) and 2) is evaluated (in particular, why rest-01 and rest-02?) and algebraically added, if at all, to 3) and 4).
>>
>> I could try to imagine what I am unable to find described in tutorial pdf (otherwise I do not see any README), but a clarification here might avoid taking wrong routes.
>>
>> thanks
>> francesco pietra
>>
>>
>
>
>
>
>
> --
> Giacomo Fiorin
> Associate Professor of Research, Temple University, Philadelphia, PA
> Contractor, National Institutes of Health, Bethesda, MD
> http://goo.gl/Q3TBQU <http://goo.gl/Q3TBQU>
> https://github.com/giacomofiorin <https://github.com/giacomofiorin>
>

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