[gmx-users] mobile ligand with intermolecular interactions

Ahmet Yildirim ahmedo047 at gmail.com
Mon Nov 13 07:49:37 CET 2017


Hi,

Let me take that in reverse order:
>
> Note that choosing appropriate atoms to apply restraints is not a trivial
> matter, and results can vary depending on the choices made.
>
I know.

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?
>

The dihedrals are almost the same in both the state A and state B (except
for the first one) when the [dihedrals] or [dihedral_restraints] is used.
Please see the results https://www.dropbox.com/s/rdw6
lg0c4xviufk/dih.pdf?dl=0

I think there is bug?

On the other hand, the pymol and GROMACS calculate differently the first
target dihedral angle between 1587, 1581, 1579 and 14 atoms, respectively
-155 and 66. I don't know why? That is strange? Note that I used -155
degrees obtained from pymol as a target value of the first dihedral in the
simulation. The other two target dihedrals are the same for both pymol and
GROMACS.

Thanks.

On 13 November 2017 at 01:55, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> 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
>>>> <https://maps.google.com/?q=the+eq.+4.84+in+the+manual+will+be+equal&entry=gmail&source=g>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
>
> ==================================================
>
> --
> Gromacs Users mailing list
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-- 
Ahmet Yildirim


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