[gmx-users] Umbrella sampling along a dihedral angle

[Justin Lemkul]

On 12/27/14 1:50 PM, Nash, Anthony wrote:
> Hi Justin,
>
> I think I've shot myself in the foot and I'm trawling the gromacs manual with little success at the moment. I'm trying to define my [ dihedral_restraint ] over my ligand-enzyme complex. The topology of the ligand is in one .itp file and the topology of the enzyme is in a separate .itp file. Therefore, in my top level topology file (system.top) I have:
>
> #include "../enzyme.itp"
> #include "../ligand.itp"
>
> Typically if I want restraints to help equilibrate the system I would just define a posre_NAME.itp with the respective force constants beneath each #include directive. But given that each topology file starts with atom 1 I am a bit unsure how I can define a set of restraints over two topology files.
>
> Can this be done? I'm really hoping I won't need to clump all topologies into one big file.
>

Restraints are always numbered with respect to the [moleculetype] to which they 
apply.  As an example:

http://www.gromacs.org/Documentation/Errors#Atom_index_n_in_position_restraints_out_of_bounds

If your (pseudo)dihedral spans the protein and the ligand, the only way to 
proceed with a restraint is to have a merged [moleculetype] of protein and 
ligand.  They simply cannot be in separate topologies in this case.

-Justin

> Thanks as ever,
> Anthony
>
>
>
> Dr Anthony Nash
> Department of Chemistry
> University College London
> ________________________________________
> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se [gromacs.org_gmx-users-bounces at maillist.sys.kth.se] on behalf of Justin Lemkul [jalemkul at vt.edu]
> Sent: 27 December 2014 14:49
> To: gmx-users at gromacs.org
> Subject: Re: [gmx-users] Umbrella sampling along a dihedral angle
>
> On 12/26/14 6:11 PM, Nash, Anthony wrote:
>> Dear Gromacs community,
>>
>> Using enforced rotation potentials I have generated a really smooth rotation
>> of my ligand the catalytic binding domain of my protein. I then put together
>> a simple perl script to calculate the dihedral angle of four particular atoms
>> at each time step using g_angle. Taking a 6 degree interval (for a total of
>> 60 windows to span the 360 degree rotation) I modified the topology with a [
>> dihedral_restraint ] with the respective dihedral angle for that particular
>> configuation. I plan on then running each window for 10 ns to begin with
>> (according to the PMF profile I can add more time). It is from this point
>> where I am a little stuck.
>>
>> I have gone through a number of posts going back to 2011 with regards to
>> using umbrella sampling along a dihedral angle reaction coordinate. The
>> precise post was from Justin:
>>
>> "You'll have to build various configurations that correspond to different
>> dihedral angles (which form the sampling windows), then restrain them.
>>
>> The energy attributed to the restraints is then stored in the .edr file. From
>> these energies, you should be able to construct the energy curve over the
>> sampling windows. There are examples of this in the literature, so I suspect
>> you should be able to find some demonstrations of how it's applied."
>>
>> I was wondering whether gromacs now support this procedure natively? I
>> noticed g_wham has an option -cycl for dihedrals but I am still not sure how
>> this fits in with the traditional gromacs means of generating pull force
>> output as I have only been using distance based rather than angular based
>> umbrella sampling.
>>
>
> g_wham is still only really designed to process the output from the pull code,
> not any generalized restraint.  That would be a nice features, but AFAIK it is
> not in the pipeline.  You can de-bias the results like I suggested above, but
> it's probably more work than it's worth.  I would suggest just using Alan
> Grossfield's WHAM implementation.  There, you just need to provide the raw
> numbers (in this case, the dihedral values) and the force constants used.  It
> will then give you your PMF.  We have done this recently; it is very easy.
>
> -Justin
>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
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-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==================================================