[gmx-users] mobile ligand with intermolecular interactions

Justin Lemkul jalemkul at vt.edu
Sun Nov 12 23:56:00 CET 2017



On 11/10/17 11:59 PM, Ahmet Yildirim wrote:
> Hi,
>
> Just tested it. The [ dihedral_restraints ] didn't help. The RMSD of the
> ligand is the same when the [ dihedral_restraints ] or [ dihedrals ] is
> used at end of the complex topology file. This is a bug?

I doubt there's a bug. I tested this feature a lot myself and have used 
it. How different are the dihedrals in the B-state vs. the A-state, and 
how much do they differ from the target values? Note that choosing 
appropriate atoms to apply restraints is not a trivial matter, and 
results can vary depending on the choices made.

-Justin

>  From my first mail:
>
>> I think [ dihedral_restraints ] will be the same as [ dihedrals ] because
>> the eq. 4.84 in the manual will be equal to 4.61 if dphiA and dphiB are
>> taken as 0 (zero), right?
>
> Checked also the position of the ligand during the simulation on the VMD.
> It is very mobile in the decoupled state as I said in the previous mail.
>
> *First test:*
> [ intermolecular_interactions ]
> [ bonds ]
> ; ai     aj    type   bA      kA     bB      kB
>   1391    2615  6      0.654   0.0    0.654   4184.0
>
> [ angles ]
> ; ai     aj    ak     type    thA      fcA        thB      fcB
>   1393   1391   2615   1       88.8     0.0        88.8     41.84
>   1391   2615   2614   1       32.9     0.0        32.9     41.84
>
> [ dihedrals ]
> ; ai     aj    ak    al    type     thA      fcA       thB      fcB
>   1410  1393  1391  2615    2       -159.7    0.0    -159.7    41.84
>   1393  1391  2615  2614    2        122.6    0.0     122.6    41.84
>   1391  2615  2614  2610    2         12.8    0.0      12.8    41.84
>
> *Second test:*
> [ intermolecular_interactions ]
> [ bonds ]
> ; ai     aj    type   bA      kA     bB      kB
>   1391    2615  6      0.654   0.0    0.654   4184.0
>
> [ angles ]
> ; ai     aj    ak     type    thA      fcA        thB      fcB
>   1393   1391   2615   1       88.8     0.0        88.8     41.84
>   1391   2615   2614   1       32.9     0.0        32.9     41.84
>
> [ dihedral_restraints ]
> ;   ai    aj    ak    al  type    phiA     dphiA  fcA    phiB      dphiB
> fcB
>   1410  1393  1391  2615     1    -159.7   0.0    0.0    -159.7    0.0
> 41.84
>   1393  1391  2615  2614     1     122.6   0.0    0.0     122.6    0.0
> 41.84
>   1393  1391  2615  2614     1      12.8   0.0    0.0     12.8     0.0
> 41.84
>
> On 10 November 2017 at 22:36, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>> On 11/10/17 2:21 PM, Ahmet Yildirim wrote:
>>
>>> Dear users,
>>>
>>> I add the following [ intermolecular_interactions ] section into the
>>> topology file of protein-ligand complex for free energy calculations.
>>> Unfortunately this setting doesn't provide me what I want in the decoupled
>>> state. The ligand in the decoupled state is very mobile compared to the
>>> coupled state. It means that the conformational sampling of the ligand in
>>> the decoupled state is quite different from the coupled state. That is not
>>> expected of course. Any suggestions as to why this might be?
>>>
>>> Do you think that there is something wrong with the following settings,
>>> e.g. [ dihedrals ] part?
>>>
>> Yes, because you're setting [dihedrals] as if they were restraints.
>> Dihedrals have a multiplicity, phase angle (not the angle you want it to
>> be, it's the shape and position of the minima in the function) and a force
>> constant. So mdrun is doing what you're telling it, but what you're telling
>> it doesn't make physical sense.
>>
>> [ intermolecular_interactions ]
>>> [ bonds ]
>>> ; ai     aj    type   bA      kA     bB      kB
>>>    1391    2615  6      0.654   0.0    0.654   4184.0
>>>
>>> [ angles ]
>>> ; ai     aj    ak     type    thA      fcA        thB      fcB
>>>    1393   1391   2615   1       88.8     0.0        88.8     41.84
>>>    1391   2615   2614   1       32.9     0.0        32.9     41.84
>>>
>>> [ dihedrals ]
>>> ; ai     aj    ak    al    type     thA      fcA       thB      fcB
>>>    1410  1393  1391  2615    2       -159.7    0.0    -159.7    41.84
>>>    1393  1391  2615  2614    2        122.6    0.0     122.6    41.84
>>>    1391  2615  2614  2610    2         12.8    0.0      12.8    41.84
>>>
>>>
>>> Should I use the following [ dihedral_restraints ] part instead of the
>>> above [ dihedrals ] part?
>>>
>> Yes, this would probably accomplish what you want.
>>
>> -Justin
>>
>> [ dihedral_restraints ]
>>> ;   ai    aj    ak    al  type    phiA     dphiA  fcA    phiB      dphiB
>>> fcB
>>>    1410  1393  1391  2615     1    -159.7   0.0    0.0    -159.7    0.0
>>> 41.84
>>>    1393  1391  2615  2614     1     122.6   0.0    0.0     122.6    0.0
>>> 41.84
>>>    1393  1391  2615  2614     1      12.8   0.0    0.0     12.8     0.0
>>> 41.84
>>>
>>> I think [ dihedral_restraints ] will be the same as [ dihedrals ] because
>>> the eq. 4.84 in the manual will be equal to 4.61 if dphiA and dphiB are
>>> taken as 0 (zero), right?
>>>
>>>
>>> Thanks in advance
>>>
>>>
>> --
>> ==================================================
>>
>> Justin A. Lemkul, Ph.D.
>> Assistant Professor
>> Virginia Tech Department of Biochemistry
>>
>> 303 Engel Hall
>> 340 West Campus Dr.
>> Blacksburg, VA 24061
>>
>> jalemkul at vt.edu | (540) 231-3129
>> http://www.biochem.vt.edu/people/faculty/JustinLemkul.html
>>
>> ==================================================
>>
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>
>

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

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

303 Engel Hall
340 West Campus Dr.
Blacksburg, VA 24061

jalemkul at vt.edu | (540) 231-3129
http://www.biochem.vt.edu/people/faculty/JustinLemkul.html

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



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