[gmx-users] Contraints on both angles and dihedrals

Wed May 9 13:13:55 CEST 2018

On 5/9/18 7:08 AM, Ahmet Yildirim wrote:
> Hi,
>
> The flexibility of the ligand due to its internal motions is a big issue
> when I turn off protein-ligand interactions in the decoupled state (state
> 1). Applying Boresch's restraints between the protein and ligand, applying
> positional retraints on all the atoms of the ligand or adding dihedral
> restraints is not sufficient to get the rigidified ligand in the case that
> the ligand is very flexible.  So, if the ligand were quite rigid, the
> target system (state 1) would be sufficiently similar to the reference
> system (state 0). For instance, the intersection of the work distributions
> of the forward (0-->1) and backward (1-->0) state would provide the
> accurate estimates of free energy...

Treating the ligand as fully rigid in this case is not a way to correct 
this problem, because then you're making an assumption that a fixed pose 
is the only one that's relevant.

For large, flexible ligands, alchemical transformations can be 
cumbersome if not impossible. Try a different approach, like computing a 
PMF with the pull code or doing MM/PBSA calculations.

-Justin

> If GROMACS have the ability to constraint all the internal coordinates of
> the ligand, then the cost of the angle, bond and dihedral constraints can
> be calculated with an extra step. That is easy.
>
> Do you have any plans for the implementation of such a feature to the next
> version of GROMACS-2018.1? :)
>
>
>
>
> On 9 May 2018 at 11:36, Mark Abraham <mark.j.abraham at gmail.com> wrote:
>
>> Hi,
>>
>> Of what would that be a good physical model?
>>
>> Mark
>>
>> On Wed, May 9, 2018, 10:07 Ahmet Yildirim <ahmedo047 at gmail.com> wrote:
>>
>>> Hi,
>>>
>>> With stiff restraints using standard GROMACS versions I couldn't get what
>>> I want. If Developers implement some like this:
>>> contraints-grps = ligand
>>> constrains = all-bonds all-angles all-dihedrals
>>>
>>> it would be wonderful :)
>>>
>>>> On 9 May 2018, at 10:56, Felipe Merino <
>>> felipe.merino at mpi-dortmund.mpg.de> wrote:
>>>> Hi,
>>>>
>>>> I guess you can always get a similar final result using some stiff
>>> restraints with gromacs/plumed.
>>>> Best
>>>>
>>>> Felipe
>>>>
>>>>
>>>>> On 09/05/18 09:48, Ahmet Yildirim wrote:
>>>>> Hi,
>>>>>
>>>>> I am facing with the same problem... Unfortunately GROMACS does not
>> have
>>>>> the capability to constraint all the internal coordinates (bond
>> lengths,
>>>>> bond angles and dihedral angles) of a certain group (e.g. ligand) in
>> the
>>>>> simulation system. Hope that Developers will take into consideration
>> the
>>>>> implementation of such a feature to the next version :)
>>>>>
>>>>>
>>>>>
>>>>>> On 8 May 2018 at 14:23, Mark Abraham <mark.j.abraham at gmail.com>
>> wrote:
>>>>>> Hi,
>>>>>>
>>>>>> There is no general support for rigid body dynamics in GROMACS.
>>>>>>
>>>>>> Mark
>>>>>>
>>>>>>> On Tue, May 8, 2018, 12:52 Qasim Pars <qasimpars at gmail.com> wrote:
>>>>>>>
>>>>>>> Dear users,
>>>>>>>
>>>>>>> I would like to constraint all the angles and dihedrals of a ligand
>> to
>>>>>>> make it rigid but Gromacs does not have this capability for the
>>>>>> dihedrals.
>>>>>>> However, the angle and dihedral restraints do not make it rigid as I
>>>>>> want,
>>>>>>> as it is very flexible.
>>>>>>>
>>>>>>> Do you have an idea on how I can make the ligand rigid using
>> gromacs?
>>>>>>> Thanks in advance,
>>>>>>> --
>>>>>>> Gromacs Users mailing list
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>>>>>> --
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>>>>>
>>>> --
>>>> Felipe Merino,
>>>> Max Planck Institute for Molecular Physiology
>>>> Department of Structural Biochemistry
>>>> Otto-Hahn-Str. 11
>>>> 44227 Dortmund
>>>> Phone: +49 231 133 2307
>>>>
>>>> ORCID:  https://orcid.org/0000-0003-4166-8747
>>>> Publons: https://publons.com/a/1305699/
>>>> Researchgate: https://www.researchgate.net/profile/Felipe_Merino
>>>>
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>

-- 
==================================================

Justin A. Lemkul, Ph.D.
Assistant Professor
Virginia Tech Department of Biochemistry

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