[gmx-users] Doubts about g_lie and g_bar

[Mark Abraham]

Hi,

I can't, since I only know in vague terms how LIE is intended to work.
Sounds like you should start by reading the paper that introduced LIE.

Mark

On Mon, May 15, 2017 at 4:28 PM Varvdekar Bhagyesh Rajendra <
bhagyesh.varvdekar at research.iiit.ac.in> wrote:

> Hi Mark,
>
> Thank you for replying.
> I would be grateful if you could please answer the doubts I have asked in
> my previous emails.
>
> Thank you,
> Bhagyesh
>
> ----- Original Message -----
> From: "Mark Abraham" <mark.j.abraham at gmail.com>
> To: gmx-users at gromacs.org
> Sent: Monday, May 15, 2017 7:25:43 PM
> Subject: Re: [gmx-users] Doubts about g_lie and g_bar
>
> Hi,
>
> On Sat, May 13, 2017 at 5:18 PM Varvdekar Bhagyesh Rajendra <
> bhagyesh.varvdekar at research.iiit.ac.in> wrote:
>
> > Dear all,
> >
> > I have tried to find Delta G of Binding using g_lie and g_bar from the
> > following systems (Protein+Ligand with ligand = chain B):
> > PDB Ids: 1CDL, 1CKK, 1NIW, 2L7L, 2o60.
> >
> > I have encountered following 2 doubts while doing so:
> >
> > 1. This doubt may have been answered in the past threads but I couldn't
> > find a precise answer for it. So, I would appreciate if this is answered
> > here again in more details. I have used PME in the production runs of my
> > systems for finding Delta G_Binding using g_lie. But many threads on
> > Gromacs forum warn against it and advise to rerun the whole trajectory
> > using Reaction field Zero, but the cutoff for this rerun is not clearly
> > given. Some threads say a cutoff with large cutoff using RF-0 is
> necessary.
> > Can anyone please answer as to what cutoff(Relative to the system) should
> > be given while re-running the trajectory and what all changes have to be
> > done in the original mdp file(which uses PME). Also, a brief explanation
> > for the whole process for the need of the re-run would be beneficial.
> > Following are the changes I made after studying the past threads:
> >
> >
> ------------------------------------------------------------------------------------------------------------------------
> > ;; With PME  ;;;                                     | ;; Re-Run without
> > PME ;;
> >
> >
> -------------------------------------------------------------------------------------------------------------------------
> >  ; Neighborsearching                                 |  ;
> Neighborsearching
> >   ns_type     = grid      ; search neighboring grid  |  ns_type     =
> > grid      ; search neighboring grid cells
> >   nstlist     = 5         ; 10 fs                    |  nstlist     = 5
> >      ; 10 fs
> >   rlist       = 0.9       ; short-range neighborlist |  rlist       = 1.2
> >      ; short-range neighborlist cutoff (nm)
> >   rcoulomb    = 0.9       ; short-range electrostatic|  rcoulomb    = 0.9
> >      ; short-range electrostatic cutoff (in nm)
> >   rvdw        = 1.4       ; short-range van der Waals|  rvdw        = 1.4
> >      ; short-range van der Waals cutoff (in nm)
> >                                                      |
> > ; Electrostatics                                     | ; Electrostatics
> > coulombtype     = PME                                | coulombtype  =
> > Reaction-Field-zero
> >                                                      | epsilon_rf
> =  0
> >
> >
> ---------------------------------------------------------------------------------------------------------------------------
> >
>
> IMO these choices should follow from your understanding of the method that
> you are implementing, e.g. as reported in peer-reviewed publications, not
> just mailing list threads or tutorials. That way you have some confirmation
> that the method was thought reasonable, and produced some kind of result.
>
> 2. Free Energy tutorials of Gromacs suggest using oriental restraints
> > and/or distance restraints on protein-ligand systems for calculating
> Delta
> > G_Binding using g_bar. But the exact details are not given on the
> website.
> > One can see that in my systems the protein is fully surrounding the
> ligand
> > except two entrances. So, I ask if distance and/or oriental constraint is
> > necessary to keep from floating it away. If yes, can anyone suggest some
> > simple ways for doing so in Gromacs. I found some research papers who
> > employ gruesome techiques of finding the correct atoms to constraint in
> the
> > ligand (for eg.Theoretical Study of the Binding Profile of the Allosteric
> > Modulator NS-1738 with a Chimera Structure of the α 7 Nicotinic
> > Acetylcholine Receptor).
> >
>
> The [intermolecular_interactions] directive introduced in recent GROMACS
> versions is useful for such restraints, ie. when you want to refer to atoms
> in different [moleculetypes], and can do so with global atom numbers.
>
> Mark
>
> I would be grateful if you could answer the above doubts.
> >
> > Thanking you in anticipation,
> >
> > Best Regards,
> >
> > Bhagyesh Varvdekar,
> > Undergrad student,
> > IIIT Hyderabad, India.
> > --
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