[gmx-users] mobile ligand with intermolecular interactions

[Justin Lemkul]

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

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