[gmx-users] ligand-protein distance restraint

[chris.neale at utoronto.ca]

Mark's suggestion of a hybrid [molecule] section is a good one. Please  
note the need to then include disre=simple in your .mdp file. Mark has  
previously posted an enhancement request for a grompp warning if you  
forget disre=simple in the .mdp file response to some confusion that I  
previously had, but I am unsure if this has been incorporated into  
v4.0.3.

A currently available alternative is to utilize the pull code (see the  
manual).

The requirement that distance restraints be intra-molecular, while  
obviously true and seemingly important for .top feasibility based on  
separate .itp files, is rather bothersome. Is it not possible,  
developers, to include some type of pre-processing that would allow  
inter-molecular distance restraints? Perhaps by preprocessing the .top  
and .itp files into new files prior to their input to the existing  
grompp structure? It seems that this might be easier now that grompp  
does not rely on cpp and the grompp preprocessor could now, in theory,  
do any type of preprocessing.

Chris.

Pathumwadee Intharathep wrote:
> Dear gmx-users,
>  Do you know how to make distance restraint between ligand and  
> protein in gromacs?
> I have a chain of protein binds with 4 drugs in water-lipid box, the  
> topology put below..
>
> ;       File 'top.top' was generated; Include forcefield parameters
> ;
> #include "/home/bio001/02_saow/gromacs_top/jit/top/ffgmx.itp"
> #include "/home/bio001/02_saow/gromacs_top/jit/popc.itp"

You can avoid the need to specify particular directories each time
through careful use of the GMXLIB environment variable, or using
"include = -I /some/dir" in your .mdp file. See
http://wiki.gromacs.org/index.php/Include_File_Mechanism

You should also refrain from using ffgmx, as it's been deprecated for
ages now.

> ; Include chain topologies
> #include "1add_H/0H_addH1.top"              ;protein atom 1-1615
> #include "disre.itp"                                      ; distance  
> restraint topology file
> #include "rimq1_top.itp"                              ;ligand  
> topology file atom 1-16
> ; Include water topology
> #include "/home/bio001/02_saow/gromacs_top/jit/top/flexspc.itp"
> #ifdef POSRES_WATER
> ; Position restraint for each water oxygen
> [ position_restraints ]
> ;  i funct       fcx        fcy        fcz
>    1    1       1000       1000       1000
> #endif
> ; Include generic topology for ions
> #include "/home/bio001/02_saow/gromacs_top/jit/top/ions.itp"
> [ system ]
> ; Name
> Protein
> [ molecules ]
> ; Compound        #mols
> Protein_A             1
> RIM                      4
> POPC                  74
> SOL                   3763
> Cl                       8
>
>  ------------------------------------------
>
> detailed in "disre.itp" file is
> [ distance_restraints ]
>
>      195   1628   1   1     1   0.25 0.35 0.40 1.0
>
>      195    563   1   1     1   0.25 0.35 0.40 1.0
>
>      598   1644   1   1     1   0.25 0.35 0.40 1.0
>
>      598    966   1   1     1   0.25 0.35 0.40 1.0
>
>     1001   1660   1   1     1   0.25 0.35 0.40 1.0
>
>     1001    369   1   1     1   0.25 0.35 0.40 1.0
>
>     1404   1676   1   1     1   0.25 0.35 0.40 1.0
>
>     1404    160   1   1     1   0.25 0.35 0.40 1.0
>
>
> The error occur after grompp run is..
>
>  ?Fatal error: [ file "../disre.itp", line 2 ]:
>
>              Atom index (1628) in distance_restraints out of bounds (1-1615)?
>
>  It seems to be that the atoms from ligand (rimq1_top.itp) topology  
> was not known.
>
> My question is Q1: Where I should put ?disre.itp? in topology file  
> that it can recognize the atom from both protein (0H_addH1.top) and  
> ligand (rimq1_top.itp) topology files.

Distance restraints may only be intra-molecular. Thus you will need to
make a hybrid [molecule] section that includes your protein and all of
its distance-restrained ligands and #include "disre.itp" at the end of
that [molecule] section.

Mark