[gmx-users] Gromacs Relative Free Energy Calculation Issue

[Guanglin Kuang]

I am sorry the attachments cannot be seen.
The attachments are now available through this Google Drive link:
https://drive.google.com/open?id=0B8f0-zVoaBXNZUpuM2ttNWQ1QUE

Best regards!
Guanglin

-----Original Message-----
From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se [mailto:gromacs.org_gmx-users-bounces at maillist.sys.kth.se] On Behalf Of Mark Abraham
Sent: Monday, October 03, 2016 10:00 PM
To: gmx-users at gromacs.org; gromacs.org_gmx-users at maillist.sys.kth.se
Subject: Re: [gmx-users] Gromacs Relative Free Energy Calculation Issue

Hi,

The list cannot accept attachments, so if you would like to share files, please do so via a file-sharing service, and post the links you wish to share :-)

Mark

On Mon, Oct 3, 2016 at 9:57 PM Guanglin Kuang <guanglin at kth.se> wrote:

> Dear Gromacs users,
>
> Has any of you managed to use Gromacs to do relative free energy 
> calculations?  I have some technical questions that would need your 
> suggestions.
>
> I am trying to reproduce the Amber free energy calculation using PMEMD 
> ( http://ambermd.org/tutorials/advanced/tutorial9/#overview).
>
> First, I generated the topology and coordinate files of the ligands 
> (benzene and phenol) using alchemistry_setup.py, developed by Dr. 
> David Mobley (https://github.com/MobleyLab/alchemical-setup), as well 
> as antechamber with AM1/BCC charge.
>
> Then I set up the mdp file and topology file for relative free energy 
> calculations. I used the single topology together with the one-step 
> and three-step transformations, respectively. Please have a look at 
> the relevant files  attached for the details.
>
> Finally, I used g_bar to calculate the free energy 
> (alchemistry_analysis.py can give similar results). From the results I 
> found that one-step transformation can give good results, only if some 
> restraints are applied to the protein-ligand complex, because I found 
> that benzene/phenol are not strong binders to lyszome, and would drift 
> around in the binding pocket, thus give poor results deviating from 
> experimental data. However, in the three-step strategy, the results 
> are much worse, this is probably due to the fact that a dual topology 
> is used in Amber but a single topology is used in Gromacs (my case), 
> we may not be able to do the changes directly (as shown in the attached topology files).
>
> Even though one-step transformation seems to give a better result in 
> this case, it may be due to luck, because it is suggested that 
> one-step transformation is usually not as good as three-step 
> transformation, and can even give misleading results in some occasions (what occasions?).
>
> Therefore, could any experienced users of relative free energy 
> calculation have a look at my set-up and point out the problems? I 
> would appreciate any improvement to the set-up!
>
> Thank you!
>
>
> ----------------------------------------------------------------------
> ----------------------------------------------------------------------
> ---------------
> Best Regards!
> Guanglin Kuang
> KTH-Royal Institute of Technology
> School of Biotechnology
> Division of Theoretical Chemistry & Biology
>
> --
> Gromacs Users mailing list
>
> * Please search the archive at
> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before 
> posting!
>
> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>
> * For (un)subscribe requests visit
> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or 
> send a mail to gmx-users-request at gromacs.org.
--
Gromacs Users mailing list

* Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting!

* Can't post? Read http://www.gromacs.org/Support/Mailing_Lists

* For (un)subscribe requests visit
https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-request at gromacs.org.