[gmx-users] mobile ligand with intermolecular interactions

Justin Lemkul jalemkul at vt.edu
Tue Nov 14 03:38:04 CET 2017



On 11/13/17 3:00 AM, Ahmet Yildirim wrote:
> Sorry. The pymol and GROMACS give the same results for every three target
> dihedrals. The updated results are here:
> https://www.dropbox.com/s/7qgn7qa4rf2yc14/dih.pdf?dl=0
>
> The results show that the average dihedrals are almost the same in both the
> state A and state B for both [dihedrals] or [dihedral_restraints]. I think
> this is normal?

Yes, because the purpose of selectively turning on the additional bond 
or restraint potential is to enforce the original geometry. Your results 
look fine to me, probably you just need a slightly larger force constant.

-Justin

> On 13 November 2017 at 09:49, Ahmet Yildirim <ahmedo047 at gmail.com> wrote:
>
>> 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
>>>>>
>>>>> ==================================================
>>>>>
>>>>> --
>>>>> Gromacs Users mailing list
>>>>>
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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
>>
>
>

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

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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