[gmx-developers] free energy calculations with restraints

Thu Jan 9 07:20:26 CET 2014

Hi,

Can those who were keen on this feature (David Mobley? Michael Shirts?) for
intermolecular bonded interactions please test it? It's pretty discouraging
to have people claim they've wanted something for years and then have four
months pass without feedback on whether Berk's effort does what they really
want! Please see https://gerrit.gromacs.org/#/c/2566/

Thanks,

Mark

On Mon, Sep 23, 2013 at 1:10 AM, Mark Abraham <mark.j.abraham at gmail.com>wrote:

> Please can those who have been keen on the feature for which Berk
> kindly wrote some code let us know whether they plan to test it some
> time soon?
>
> Mark
>
> On Sun, Sep 1, 2013 at 5:51 AM, Shirts, Michael (mrs5pt)
> <mrs5pt at eservices.virginia.edu> wrote:
> > Great, this is exactly the documentation needed to test it.
> >
> > So if one wants to use these as free energy-dependent restraining terms,
> > which correspond to the restraint part of the lambda vector, not the
> bonded
> > part, then one just needs to make sure that one uses the restraint bonded
> > types, not normal bonded types.
> >
> > I do not there are no explicit angle restraint terms for three atoms.
>  Can
> > the four-atom angle_restraint be used as a three angle restraint by
> > repeating one of the pairs?
> >
> > Best,
> > ~~~~~~~~~~~~
> > Michael Shirts
> > Assistant Professor
> > Department of Chemical Engineering
> > University of Virginia
> > michael.shirts at virginia.edu
> > (434)-243-1821
> >
> >
> >> From: Berk Hess <hess at kth.se>
> >> Date: Sat, 31 Aug 2013 09:31:32 +0200
> >> To: "michael.shirts at virginia.edu" <michael.shirts at virginia.edu>,
> Discussion
> >> list for GROMACS development <gmx-developers at gromacs.org>
> >> Subject: Re: [gmx-developers] free energy calculations with restraints
> >>
> >> Hi,
> >>
> >> I haven't documented it yet, as I want to be sure this is the
> >> functionality people were asking for.
> >> I didn't add new interaction types, as we can reuse all the grompp and
> >> mdrun code and we don't need even more interaction types and requests
> >> for support. At the mdrun level there is no difference between the usual
> >> intramolecular and the new intermolecular interactions, except for the
> >> graph code, as that only ensure intramolecular interactions don't need
> >> pbc treatment.
> >> It is really simple, here is a small example .top file:
> >>
> >> ....
> >>
> >> [ system ]
> >> protein+ligand+water
> >>
> >> [ molecules ]
> >> protein 1 ; 2000 atoms, nr 1-2000
> >> ligand 1 ; 10 atoms, nr 2001-2010
> >> water 10000
> >>
> >> [ intermolecular-interactions ]
> >> ; any bonded type(s) using 2 atoms or more which is a potential (e.g. no
> >> vsite, constraints) and does not generate exclusions can follow
> >>
> >> [ angles ]
> >> 803 804 2002 1   30.0 100.0 ; angle potential between 2 protein atoms
> >> and 1 ligand atom
> >>
> >> ...
> >>
> >> Cheers,
> >>
> >> Berk
> >>
> >> On 08/30/2013 11:51 PM, Shirts, Michael (mrs5pt) wrote:
> >>> Berk, just following up on the requests below to make it easier to
> test the
> >>> code:
> >>>
> >>> Thanks!
> >>> ~~~~~~~~~~~~
> >>> Michael Shirts
> >>> Assistant Professor
> >>> Department of Chemical Engineering
> >>> University of Virginia
> >>> michael.shirts at virginia.edu
> >>> (434)-243-1821
> >>>
> >>>
> >>>> From: "Michael R. Shirts" <mrs5pt at eservices.virginia.edu>
> >>>> Reply-To: <michael.shirts at virginia.edu>
> >>>> Date: Wed, 21 Aug 2013 10:09:55 -0400
> >>>> To: Discussion list for GROMACS development <
> gmx-developers at gromacs.org>
> >>>> Subject: Re: [gmx-developers] free energy calculations with restraints
> >>>>
> >>>> Hi, Berk-
> >>>>
> >>>> * Would it be possible to post (perhaps to redmine?) some example
> files of
> >>>> calling usage?
> >>>>
> >>>> * Perhaps you can provide a bit more of the logic for how this is
> >>>> implemented? I was expecting a new interaction_function type, but
> this seems
> >>>> to be done somewhat differently, and I'm not quite sure how it works
> -- I
> >>>> suspect other people will be confused as well.
> >>>>
> >>>> Best,
> >>>> ~~~~~~~~~~~~
> >>>> Michael Shirts
> >>>> Assistant Professor
> >>>> Department of Chemical Engineering
> >>>> University of Virginia
> >>>> michael.shirts at virginia.edu
> >>>> (434)-243-1821
> >>>>
> >>>>
> >>>>> From: Berk Hess <hess at kth.se>
> >>>>> Reply-To: Discussion list for GROMACS development
> >>>>> <gmx-developers at gromacs.org>
> >>>>> Date: Wed, 21 Aug 2013 17:47:42 +0200
> >>>>> To: Discussion list for GROMACS development <
> gmx-developers at gromacs.org>
> >>>>> Subject: Re: [gmx-developers] free energy calculations with
> restraints
> >>>>>
> >>>>> Hi,
> >>>>>
> >>>>> I pushed up a patch to gerrit (master) which is complete afaik, but
> with
> >>>>> a change as extensive as this, there is always a chance I overlooked
> >>>>> something:
> >>>>> https://gerrit.gromacs.org/#/c/2566/
> >>>>>
> >>>>> Please try and report back!
> >>>>>
> >>>>> Cheers,
> >>>>>
> >>>>> Berk
> >>>>>
> >>>>> On 08/21/2013 10:08 AM, Mark Abraham wrote:
> >>>>>> Hi,
> >>>>>>
> >>>>>> I've been following with interest, and Berk and I discussed these
> >>>>>> issues yesterday. I'd been afraid there would be artifacts of
> >>>>>> "[moleculetype] is self-contained and exclusive" all through the
> code,
> >>>>>> but Berk seems pretty sure that's not the case. The kind of
> >>>>>> [intermolecule-interactions] suggested above sounds great to me, as
> a
> >>>>>> potential building block for all sorts of things.
> >>>>>>
> >>>>>> Mark
> >>>>>>
> >>>>>> On Tue, Aug 20, 2013 at 7:12 PM, David Mobley <dmobley at gmail.com>
> wrote:
> >>>>>>> Yes, I'm very enthusiastic about adding defined intermolecular
> restraints
> >>>>>>> using absolute atom indices. It seems like a straightforward,
> correct,
> >>>>>>> easy-to-understand way to deal with this simple problem.
> >>>>>>>
> >>>>>>> David
> >>>>>>>
> >>>>>>>
> >>>>>>>
> >>>>>>> On Tue, Aug 20, 2013 at 9:39 AM, Shirts, Michael (mrs5pt)
> >>>>>>> <mrs5pt at eservices.virginia.edu> wrote:
> >>>>>>>> The other thing I would say is that the couple-mol code is a
> little
> >>>>>>>> difficult to work with----there's known quirks, like handling the
> >>>>>>>> intramolecular dispersion in a way that's slightly off from free
> energy
> >>>>>>>> off,
> >>>>>>>> as well as some new quirks that I'll try to post about later this
> >>>>>>>> week---that it would actually be cleaner to add clearly defined
> >>>>>>>> intermolecular restraints than add complexity to the coupling
> feature.
> >>>>>>>>
> >>>>>>>> Best,
> >>>>>>>> ~~~~~~~~~~~~
> >>>>>>>> Michael Shirts
> >>>>>>>> Assistant Professor
> >>>>>>>> Department of Chemical Engineering
> >>>>>>>> University of Virginia
> >>>>>>>> michael.shirts at virginia.edu
> >>>>>>>> (434)-243-1821
> >>>>>>>>
> >>>>>>>>
> >>>>>>>>> From: Floris Buelens <floris_buelens at yahoo.com>
> >>>>>>>>> Reply-To: Floris Buelens <floris_buelens at yahoo.com>, Discussion
> list
> >>>>>>>>> for
> >>>>>>>>> GROMACS development <gmx-developers at gromacs.org>
> >>>>>>>>> Date: Tue, 20 Aug 2013 08:35:15 -0400
> >>>>>>>>> To: Berk Hess <hess at kth.se>, Discussion list for GROMACS
> development
> >>>>>>>>> <gmx-developers at gromacs.org>
> >>>>>>>>> Subject: Re: [gmx-developers] free energy calculations with
> restraints
> >>>>>>>>>
> >>>>>>>>> Hi Berk,
> >>>>>>>>>
> >>>>>>>>> I think we might have gone out of sync there - I sent the
> message below
> >>>>>>>>> before
> >>>>>>>>> reading yours from this morning. From the misplaced context it
> maybe
> >>>>>>>>> sounded
> >>>>>>>>> like I was disagreeing with your '[ intermolecular-interactions
> ]'
> >>>>>>>>> suggestion,
> >>>>>>>>> which I'm definitely not - this would clearly be preferable and
> >>>>>>>>> probably
> >>>>>>>>> useful to a wider audience.
> >>>>>>>>>
> >>>>>>>>>
> >>>>>>>>>
> >>>>>>>>> ----- Original Message -----
> >>>>>>>>> From: Berk Hess <hess at kth.se>
> >>>>>>>>> To: Floris Buelens <floris_buelens at yahoo.com>; Discussion list
> for
> >>>>>>>>> GROMACS
> >>>>>>>>> development <gmx-developers at gromacs.org>
> >>>>>>>>> Cc:
> >>>>>>>>> Sent: Tuesday, 20 August 2013, 12:04
> >>>>>>>>> Subject: Re: [gmx-developers] free energy calculations with
> restraints
> >>>>>>>>>
> >>>>>>>>> Hi,
> >>>>>>>>>
> >>>>>>>>> We could consider this.
> >>>>>>>>> I don't know how you did this now, but this would need an extra
> mdp
> >>>>>>>>> option, something like couple-group, to avoid one option with a
> moltype
> >>>>>>>>> or index group as an input.
> >>>>>>>>> Then we would also need to decide what to do with a group which
> is part
> >>>>>>>>> of one molecule of a certain moleculetype with multiple copies.
> >>>>>>>>> Disallow
> >>>>>>>>> this? Or duplicate the moltype and only modify one copy (as is
> done now
> >>>>>>>>> for qmmm)?
> >>>>>>>>>
> >>>>>>>>> Cheers,
> >>>>>>>>>
> >>>>>>>>> Berk
> >>>>>>>>>
> >>>>>>>>> On 08/20/2013 09:24 AM, Floris Buelens wrote:
> >>>>>>>>>> Hi,
> >>>>>>>>>>
> >>>>>>>>>> I would also still argue for augmenting the current
> couple-moltype
> >>>>>>>>>> functionality with this modification. I can see this is a niche
> >>>>>>>>>> requirement,
> >>>>>>>>>> which of course does speak against inclusion. But in my view the
> >>>>>>>>>> replacement
> >>>>>>>>>> code is no less elegant than the current implementation
> (modification
> >>>>>>>>>> of five
> >>>>>>>>>> self-contained functions at the pre-processing stage, maybe
> 50-odd
> >>>>>>>>>> extra
> >>>>>>>>>> lines), we can maintain full backward compatibility, and a
> single
> >>>>>>>>>> simple
> >>>>>>>>>> check will remove any potential for accidental misuse.
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>> ________________________________
> >>>>>>>>>> From: David Mobley <dmobley at uci.edu>
> >>>>>>>>>> To: Discussion list for GROMACS development
> >>>>>>>>>> <gmx-developers at gromacs.org>
> >>>>>>>>>> Cc: Floris Buelens <floris_buelens at yahoo.com>; Michael R.
> Shirts
> >>>>>>>>>> <michael.shirts at virginia.edu>
> >>>>>>>>>> Sent: Monday, 19 August 2013, 20:02
> >>>>>>>>>> Subject: Re: [gmx-developers] free energy calculations with
> restraints
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>> Hi, Berk,
> >>>>>>>>>>
> >>>>>>>>>> I agree that this solution would be the "proper" one and would
> be
> >>>>>>>>>> nice.
> >>>>>>>>>> However, it's been a long time coming (this is an issue I've
> been
> >>>>>>>>>> raising for
> >>>>>>>>>> approximately 5 years, and there's no progress; normally no one
> even
> >>>>>>>>>> answers). Currently, for the restraints I need to use, I *have*
> to
> >>>>>>>>>> merge the
> >>>>>>>>>> ligand into my protein topology, inconvenient or not. Doing
> this also
> >>>>>>>>>> means
> >>>>>>>>>> there are some features I simply can't use (couple-moltype for
> >>>>>>>>>> example).
> >>>>>>>>>>
> >>>>>>>>>> It strikes me that Floris's solution is a good interim one, in
> that it
> >>>>>>>>>> at
> >>>>>>>>>> least solves most of the typical use cases we're facing, and
> has the
> >>>>>>>>>> advantage of being *already implemented*.
> >>>>>>>>>>
> >>>>>>>>>> Is there any way we could get this into the main GROMACS, at
> least
> >>>>>>>>>> until
> >>>>>>>>>> someone gets time to implementing the "proper" solution (which
> could
> >>>>>>>>>> be
> >>>>>>>>>> years
> >>>>>>>>>> from now)?
> >>>>>>>>>>
> >>>>>>>>>> Thanks!
> >>>>>>>>>> David
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>> On Mon, Aug 19, 2013 at 1:10 AM, Berk Hess <hess at kth.se> wrote:
> >>>>>>>>>>
> >>>>>>>>>> Hi,
> >>>>>>>>>>> I fully understood this point, maybe my reply wasn't well
> structured.
> >>>>>>>>>>> I was trying to argue that the proper solution would be to
> implement
> >>>>>>>>>>> inter-molecular restraints, instead of introducing an option
> which
> >>>>>>>>>>> could me
> >>>>>>>>>>> misused. Also merging a ligand topology into your protein
> topology is
> >>>>>>>>>>> very
> >>>>>>>>>>> inconvenient. This problem with the proper solution is, of
> course,
> >>>>>>>>>>> that
> >>>>>>>>>>> someone will need to implement inter-molecular
> restraints/potentials.
> >>>>>>>>>>>
> >>>>>>>>>>> One issue used to be that we corrected molecules for PBC before
> >>>>>>>>>>> calculating
> >>>>>>>>>>> bonded interactions. But in 4.6 this is usually not faster and
> not
> >>>>>>>>>>> used any
> >>>>>>>>>>> more. That makes it easier to treat intra- and inter-molecular
> >>>>>>>>>>> interactions
> >>>>>>>>>>> the same way at the mdrun level.
> >>>>>>>>>>>
> >>>>>>>>>>> Cheers,
> >>>>>>>>>>>
> >>>>>>>>>>> Berk
> >>>>>>>>>>>
> >>>>>>>>>>>
> >>>>>>>>>>> On 08/19/2013 09:55 AM, Floris Buelens wrote:
> >>>>>>>>>>>
> >>>>>>>>>>> Hi Berk,
> >>>>>>>>>>>> I think some clarification is needed. What we're talking
> about is
> >>>>>>>>>>>> only
> >>>>>>>>>>>> relevant in the context of non-bonded interactions, typically
> >>>>>>>>>>>> between
> >>>>>>>>>>>> a
> >>>>>>>>>>>> small molecule and a protein. To access the binding affinity
> of a
> >>>>>>>>>>>> ligand
> >>>>>>>>>>>> through alchemical methods, it's useful to switch off only the
> >>>>>>>>>>>> interactions
> >>>>>>>>>>>> of the ligand with its environment while maintaining
> intra-ligand
> >>>>>>>>>>>> potentials - this is what's provided by the 'couple-moltype'
> code
> >>>>>>>>>>>> path.
> >>>>>>>>>>>>
> >>>>>>>>>>>> The limitation that we're trying to circumvent comes from the
> fact
> >>>>>>>>>>>> that as
> >>>>>>>>>>>> you scale down interactions with the environment, the ligand
> is no
> >>>>>>>>>>>> longer
> >>>>>>>>>>>> held in the binding site. To counteract this, it's necessary
> to
> >>>>>>>>>>>> perturb in
> >>>>>>>>>>>> restraining potentials as the intramolecular nonbonded
> interactions
> >>>>>>>>>>>> are
> >>>>>>>>>>>> perturbed out. The most practical method makes use of a single
> >>>>>>>>>>>> distance
> >>>>>>>>>>>> restraint, two angle and three dihedral restraints, whose
> effect can
> >>>>>>>>>>>> later
> >>>>>>>>>>>> be accounted for analytically.
> >>>>>>>>>>>>
> >>>>>>>>>>>> The current code only allows decoupling of a whole logical
> >>>>>>>>>>>> 'molecule'
> >>>>>>>>>>>> as
> >>>>>>>>>>>> specified in the topology file. This precludes the use of
> regular
> >>>>>>>>>>>> (fully
> >>>>>>>>>>>> perturbation-aware) bonded interactions. As far as I'm aware,
> the
> >>>>>>>>>>>> pull code
> >>>>>>>>>>>> doesn't provide what's required. Inter-molecular bonded
> interactions
> >>>>>>>>>>>> would
> >>>>>>>>>>>> be a great general solution but presumably won't show up any
> time
> >>>>>>>>>>>> soon.
> >>>>>>>>>>>>
> >>>>>>>>>>>> The workaround here is instead to represent two physical
> molecules
> >>>>>>>>>>>> (e.g.
> >>>>>>>>>>>> protein and ligand) as a single logical molecule (in the
> topology
> >>>>>>>>>>>> file), so
> >>>>>>>>>>>> regular bonded potentials can be applied. Current Gromacs
> doesn't
> >>>>>>>>>>>> allow the
> >>>>>>>>>>>> decoupling ('couple-moltype') code to be used in this
> scenario. My
> >>>>>>>>>>>> modification allows you to target the ligand by its residue
> name and
> >>>>>>>>>>>> get
> >>>>>>>>>>>> this functionality back.
> >>>>>>>>>>>>
> >>>>>>>>>>>> Decoupling a single residue of a multi-residue chain is indeed
> >>>>>>>>>>>> probably not
> >>>>>>>>>>>> correct in this framework (I did call it 'weird' in my last
> message
> >>>>>>>>>>>> :-) ).
> >>>>>>>>>>>> An extra check would block users from trying this.
> >>>>>>>>>>>>
> >>>>>>>>>>>> I hope that clarifies the problem we're trying to solve. I
> agree
> >>>>>>>>>>>> this
> >>>>>>>>>>>> will
> >>>>>>>>>>>> be useful a relatively small number of users, but on the
> other hand
> >>>>>>>>>>>> it's a
> >>>>>>>>>>>> very unobtrusive, self-contained modification which can
> maintain
> >>>>>>>>>>>> full
> >>>>>>>>>>>> backwards compatibility.
> >>>>>>>>>>>>
> >>>>>>>>>>>> thanks,
> >>>>>>>>>>>>
> >>>>>>>>>>>> Floris
> >>>>>>>>>>>>
> >>>>>>>>>>>>
> >>>>>>>>>>>> ----- Original Message -----
> >>>>>>>>>>>> From: Berk Hess <hess at kth.se>
> >>>>>>>>>>>> To: Floris Buelens <floris_buelens at yahoo.com>; Discussion
> list for
> >>>>>>>>>>>> GROMACS
> >>>>>>>>>>>> development <gmx-developers at gromacs.org>
> >>>>>>>>>>>> Cc:
> >>>>>>>>>>>> Sent: Monday, 19 August 2013, 9:03
> >>>>>>>>>>>> Subject: Re: [gmx-developers] free energy calculations with
> >>>>>>>>>>>> restraints
> >>>>>>>>>>>>
> >>>>>>>>>>>> Hi,
> >>>>>>>>>>>>
> >>>>>>>>>>>> There is the rotational pull code, but that might not provide
> the
> >>>>>>>>>>>> exact
> >>>>>>>>>>>> functionality you want.
> >>>>>>>>>>>> Already for some time we have been discussing inter-molecular
> >>>>>>>>>>>> interactions, by specifying molecule type, molecule index and
> atom
> >>>>>>>>>>>> index, but there are no concrete plans for implementing this
> yet.
> >>>>>>>>>>>>
> >>>>>>>>>>>> An option for decoupling part of a molecule indeed sound
> useful. But
> >>>>>>>>>>>> in
> >>>>>>>>>>>> practice you always need to replace that part by something
> else, at
> >>>>>>>>>>>> least a hydrogen, and modify some potentials of connecting
> atoms, so
> >>>>>>>>>>>> I
> >>>>>>>>>>>> don't know how generally useful such an option is.
> >>>>>>>>>>>>
> >>>>>>>>>>>> Cheers,
> >>>>>>>>>>>>
> >>>>>>>>>>>> Berk
> >>>>>>>>>>>>
> >>>>>>>>>>>> On 08/19/2013 07:56 AM, Floris Buelens wrote:
> >>>>>>>>>>>>
> >>>>>>>>>>>> I suppose that would make sense. The changes are fairly minor
> (more
> >>>>>>>>>>>> or less
> >>>>>>>>>>>> just the function convert_moltype_couple and the four
> functions it
> >>>>>>>>>>>> calls)
> >>>>>>>>>>>> and mainly consist of a bit of extra juggling with nonbonded
> >>>>>>>>>>>> exclusions
> >>>>>>>>>>>> during preprocessing. The current functionality (decouple a
> whole
> >>>>>>>>>>>> molecule)
> >>>>>>>>>>>> could be handled as a special case of the new code. A check
> for
> >>>>>>>>>>>> bonds
> >>>>>>>>>>>> to
> >>>>>>>>>>>> the rest of the structure could stop people from trying weird
> stuff
> >>>>>>>>>>>> like
> >>>>>>>>>>>> decoupling residues from a chain.
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> ________________________________
> >>>>>>>>>>>>> From: David Mobley <dmobley at gmail.com>
> >>>>>>>>>>>>> To: Floris Buelens <floris_buelens at yahoo.com>
> >>>>>>>>>>>>> Cc: Discussion list for GROMACS development
> >>>>>>>>>>>>> <gmx-developers at gromacs.org>
> >>>>>>>>>>>>> Sent: Friday, 16 August 2013, 18:30
> >>>>>>>>>>>>> Subject: Re: [gmx-developers] free energy calculations with
> >>>>>>>>>>>>> restraints
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> This does sound useful, though it would be more useful if
> this
> >>>>>>>>>>>>> could
> >>>>>>>>>>>>> be
> >>>>>>>>>>>>> implemented into the main GROMACS rather than a separate code
> >>>>>>>>>>>>> (since
> >>>>>>>>>>>>> otherwise it will go away as GROMACS is further developed).
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> Would this be a possibility going forward, devels?
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> Thanks!
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> On Fri, Aug 16, 2013 at 3:07 AM, Floris Buelens
> >>>>>>>>>>>>> <floris_buelens at yahoo.com>
> >>>>>>>>>>>>> wrote:
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> Hi David,
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> I have the same requirement as you, but I've gone about it
> slightly
> >>>>>>>>>>>>> differently. I've hacked the couple-moltype code path to
> allow
> >>>>>>>>>>>>> decoupling
> >>>>>>>>>>>>> of a specific residue (identified by name) instead of a
> molecule.
> >>>>>>>>>>>>> This
> >>>>>>>>>>>>> allows the residue of interest to be part of another
> molecule block
> >>>>>>>>>>>>> so you
> >>>>>>>>>>>>> can set up distance, angle and dihedral restraints using
> regular
> >>>>>>>>>>>>> bonded
> >>>>>>>>>>>>> interactions with full perturbation support.
> >>>>>>>>>>>>> If this is useful to you or to anyone else, let me know and
> I'll be
> >>>>>>>>>>>>> happy
> >>>>>>>>>>>>> to share.
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> best,
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> Floris
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> ________________________________
> >>>>>>>>>>>>> From: David Mobley <dmobley at gmail.com>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> To: Discussion list for GROMACS development
> >>>>>>>>>>>>> <gmx-developers at gromacs.org>
> >>>>>>>>>>>>> Sent: Friday, 14 June 2013, 21:47
> >>>>>>>>>>>>> Subject: [gmx-developers] free energy calculations with
> restraints
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> Hi, devs,
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> I'm writing with an issue relating to the interplay of new
> free
> >>>>>>>>>>>>> energy
> >>>>>>>>>>>>> features with restraints.
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> I'm very much appreciating some of the new free energy
> features in
> >>>>>>>>>>>>> gromacs, such as the 'couple-moltype' option which provides
> a way
> >>>>>>>>>>>>> to set
> >>>>>>>>>>>>> up decoupling or annihilation of a specific molecule via free
> >>>>>>>>>>>>> energy
> >>>>>>>>>>>>> calculations without having to edit the topology file
> directly.
> >>>>>>>>>>>>> This is
> >>>>>>>>>>>>> especially great when it comes to decoupling -- charge
> decoupling
> >>>>>>>>>>>>> was not
> >>>>>>>>>>>>> previously possible via topology file editing, and vdW
> decoupling
> >>>>>>>>>>>>> took
> >>>>>>>>>>>>> substantial manipulation of the topology file.
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> However, for binding free energies, my work employs
> orientational
> >>>>>>>>>>>>> restraints between the protein and ligand. I need to be able
> to
> >>>>>>>>>>>>> impose
> >>>>>>>>>>>>> both dihedral and angle restraints on angles between the
> protein
> >>>>>>>>>>>>> and
> >>>>>>>>>>>>> ligand. Currently, I do this using angle-restraints and
> >>>>>>>>>>>>> dihedral-restraints. This requires that both the protein and
> ligand
> >>>>>>>>>>>>> be
> >>>>>>>>>>>>> within the same logical 'molecule', which (unfortunately)
> means
> >>>>>>>>>>>>> that I
> >>>>>>>>>>>>> can't make use of the new free energy features above, since
> >>>>>>>>>>>>> couple-moltype has to apply to a whole molecule, not just
> part of a
> >>>>>>>>>>>>> molecule.
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> So, my I see two possible solutions to the problem, and
> hence have
> >>>>>>>>>>>>> these
> >>>>>>>>>>>>> questions:
> >>>>>>>>>>>>> 1) Can dihedral and angle restraints be applied via the pull
> code?
> >>>>>>>>>>>>> If
> >>>>>>>>>>>>> not, are there any plans to add that?
> >>>>>>>>>>>>> 2) Alternatively, what about modifying the restraints code
> so it
> >>>>>>>>>>>>> uses (or
> >>>>>>>>>>>>> at least optionally allows) absolute atom numbering, rather
> than
> >>>>>>>>>>>>> numbering within a specific molecule, thus allowing
> restraints
> >>>>>>>>>>>>> (angle-restraints and dihedral-restraints) to be applied
> between
> >>>>>>>>>>>>> 'molecules'?
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> Thanks!
> >>>>>>>>>>>>> David
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> --
> >>>>>>>>>>>>> David Mobley
> >>>>>>>>>>>>> dmobley at gmail.com
> >>>>>>>>>>>>> 949-385-2436
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>> --
> >>>>>>>>>>>>> gmx-developers mailing list
> >>>>>>>>>>>>> gmx-developers at gromacs.org
> >>>>>>>>>>>>> http://lists.gromacs.org/mailman/listinfo/gmx-developers
> >>>>>>>>>>>>> Please don't post (un)subscribe requests to the list. Use the
> >>>>>>>>>>>>> www interface or send it to
> gmx-developers-request at gromacs.org.
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>> --
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> >>>>>>>> --
> >>>>>>>> gmx-developers mailing list
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> >>>>>>>
> >>>>>>>
> >>>>>>> --
> >>>>>>> David Mobley
> >>>>>>> dmobley at gmail.com
> >>>>>>> 949-385-2436
> >>>>>>>
> >>>>>>> --
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