[gmx-users] Error in free energy calculation

[Amir Zeb]

You probably follow umbrella sampling for free energy calculation.
If it is so, you may change the position of your drug.itp file in topology
file, means that before the protein topology.
I hope this might solve your problem.

Good luck!

Amir

On Thu, Mar 16, 2017 at 2:49 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
> --
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