[gmx-users] Error in free energy calculation

[Hannes Loeffler]

On Thu, 16 Mar 2017 10:09:58 +0000
Vytautas Rakeviius <vytautas1987 at yahoo.com> wrote:

> You should try to add PLUMED (plumed.org) to GROMACS for such
> things.Bonomi, M., Branduardi, D., Bussi, G., Camilloni, C., Provasi,
> D., Raiteri, P., ... & Parrinello, M. (2009). PLUMED: A portable
> plugin for free-energy calculations with molecular dynamics. Computer
> Physics Communications, 180(10), 1961-1972. 

I'm not sure how this is helping the original request.  Does Plumed
handle the method being used here?  If not, what would the alternative
be and what would be the advantage of that?


>     On Thursday, March 16, 2017 11:50 AM, Tasneem Kausar
> <tasneemkausar12 at gmail.com> wrote: 
> 
>  Dear All
> 
> I am trying to perform free energy calculations of a protein drug
> system. I am using Gromacs-5.1.4 for this purpose. decoulpe molecule
> type i.e. drug molecule is defined in separate drug.itp file. From
> the discussions of mailing list I have found that this is not a
> problem. To obtain the equilibrium values for protein-ligand
> restraint 15 ns simulation was performed. Here is the last section of
> topology file. ; Include Position restraint file
> #ifdef POSRES
> #include "posre.itp"
> #endif
> #include "drug.itp"
> [ intermolecular_interactions ]
> [ bonds ]
> ;    i    j  type    r0A    r1A    r2A    fcA    r0B    r1B    r2B
> fcB
>   1444  3118    10    0.591  0.591  10.0  0.0    0.591  0.591  10.0
> 4184.000
> 
> [ angle_restraints ]
> ;  ai    aj    ak    al  type    thA      fcA    multA  thB      fcB
> multB
>   1431  1444  3118  1444    1    52.35    0.0    1    52.35
> 41.840    1 1444  3118  3120  3118    1  118.14    0.0    1  118.14
>   41.840    1
> 
> [ dihedral_restraints ]
> ;  ai    aj    ak    al  type    phiA    dphiA  fcA    phiB      dphiB
> fcB
>   1444  1431  1444  3118    1    -99.41  0.0    0.0    -99.41    0.0
> 41.840
>   1431  1444  3118  3120    1    17.49    0.0    0.0    17.49    0.0
> 41.840
>   1444  3118  3120  3119    1    -6.49  0.0    0.0    -6.49    0.0
> 41.840
> ; Include water topology
> #include "gromos54a7.ff/spc.itp"
> 
> #ifdef POSRES_WATER
> ; Position restraint for each water oxygen
> [ position_restraints ]
> ;  i funct      fcx        fcy        fcz
>   1    1      1000      1000      1000
> #endif
> 
> ; Include topology for ions
> #include "gromos54a7.ff/ions.itp"
> 
> [ system ]
> ; Name
> DUMM in water t= 10000.00000
> [ molecules ]
> ; Compound        #mols
> Protein_chain_A    1
> DRG                1
> SOL            17685
> 
> Is there any default position for [ intermolecular_interaction ] in
> topology file.
> Since I am using a drug.itp file for drug molecule. Numbering in itp
> file starts from 1. Is atom number in itp file needed to be modified?
> 
> 
> grompp gives many warning  and 1 error
> Back Off! I just backed up mdout.mdp to ./#mdout.mdp.9#
> 
> WARNING 1 [file em_steep_0.mdp, line 78]:
>   Unknown left-hand 'pull_geometry' in parameter file
> 
> 
> 
> WARNING 2 [file em_steep_0.mdp, line 78]:
>   Unknown left-hand 'pull_dim' in parameter file
> 
> 
> 
> WARNING 3 [file em_steep_0.mdp, line 78]:
>   Unknown left-hand 'pull_start' in parameter file
> 
> 
> 
> WARNING 4 [file em_steep_0.mdp, line 78]:
>   Unknown left-hand 'pull_init1' in parameter file
> 
> 
> 
> WARNING 5 [file em_steep_0.mdp, line 78]:
>   Unknown left-hand 'pull_ngroups' in parameter file
> 
> 
> 
> WARNING 6 [file em_steep_0.mdp, line 78]:
>   Unknown left-hand 'pull_group0' in parameter file
> 
> 
> 
> WARNING 7 [file em_steep_0.mdp, line 78]:
>   Unknown left-hand 'pull_group1' in parameter file
> 
> 
> 
> WARNING 8 [file em_steep_0.mdp, line 78]:
>   Unknown left-hand 'pull_k1' in parameter file
> 
> 
> 
> WARNING 9 [file em_steep_0.mdp, line 78]:
>   Unknown left-hand 'pull_kB1' in parameter file
> 
> 
> 
> NOTE 1 [file em_steep_0.mdp]:
>   With Verlet lists the optimal nstlist is >= 10, with GPUs >= 20.
> Note that with the Verlet scheme, nstlist has no effect on the
> accuracy of your simulation.
> 
> Setting the LD random seed to 1259182625
> Generated 226 of the 1711 non-bonded parameter combinations
> 
> -------------------------------------------------------
> Program gmx grompp, VERSION 5.1.4
> Source code file:
> /home/shahid/Software/gromacs-5.1.4/src/gromacs/gmxpreprocess/topio.c,
> line: 755
> 
> Fatal error:
> Syntax error - File complex.top, line 19956
> Last line read:
> '[ intermolecular_interactions ]'
> Invalid order for directive intermolecular_interactions
> For more information and tips for troubleshooting, please check the
> GROMACS website at http://www.gromacs.org/Documentation/Errors
> -------------------------------------------------------
> 
> Here are mdp parameters
> 
> ; Options for the decoupling
> sc-alpha                = 0.5
> sc-coul                  = no
> sc-power                = 1
> sc-sigma                = 0.3
> couple-moltype          = DRG
> couple-lambda0          = none
> couple-lambda1          = vdw-q
> couple-intramol          = no
> nstdhdl                  = 10
> ; No velocities during EM
> gen_vel                  = no
> ; options for bonds
> constraints              = all_bonds
> constraint-algorithm    = lincs
> continuation            = no
> lincs-order              = 12
> pull          = no
> pull_geometry  = distance
> pull_dim      = N N Y
> pull_start    = yes
> pull_init1    = 0.654
> pull_ngroups  = 1
> pull_group0    = a_1444
> pull_group1    = a_3118
> pull_k1        = 0.0  ; kJ*mol^(-1)*nm^(-2)
> pull_kB1      = 4184  ; kJ*mol^(-1)*nm^(-2)
> 
> since I have defined restraint parameters for protein and drug. then
> what is need of pulling code and why?
> 
> Kindly resolve the issue.
> Thanks in Advance.
> Regards