[gmx-users] Ligand coming out while trying Drug-enzyme tutorial

[Mark Abraham]

On 05/02/10 00:43, vivek sharma wrote:
> Hi Mark,
> Thanks for your response, it worked well for few molecule but not for all.
> As I mentioned first I am doing docking and then processing receptor
> through pdb2gmx and ligand through PRODRG server.
> But number of Hydrogen atoms in docked ligand and PRODRG generated
> topology are not same.

Why? How? This must be known to resolve the issue. If the docking 
program strips off all hydrogens, then look in its documentation for 
methods to build them back in after docking. You must also ensure the 
state of titratable groups is consistent.

> Although, number of Hydrogens are same in PRODRG
> generated topology and pdb file but I can't use them as they have
> modified co-ordinate than docked ligand, and the docked ligand
> coordinates can't be used as they dont have all Hydrogen atom as
> mentioned in topology file (.itp file).
> Can you suggest a way to come out of this problem.

Not without more information.

Mark

> Thanks & Regards,
> Vivek
>
> On 27 January 2010 10:40, Mark Abraham <Mark.Abraham at anu.edu.au
> <mailto:Mark.Abraham at anu.edu.au>> wrote:
>
>     On 27/01/10 15:58, vivek sharma wrote:
>
>         Hi Dallas,
>         I am trying to run MD simulation over a docked complex
>         (protein+ligand),
>         to confirm their dynamic stability in water media.
>         For the same I am using PRODRG server to generate topologies for
>         ligand
>         molecule as gromacs can generate topology for 20 standard
>         residues. As
>         mentioned in tutorial for drug-enzyme complex, I am editing the
>         .top and
>         .gro files to include the PRODRG generated files (DRGGMX.ITP in
>         .top and
>         DRGAPH.GRO in .gro file).
>         I observe that their are changes in co-ordinate of ligand after
>         processing them through PRODRG server. So these new co-ordinates for
>         ligand are placing ligand away from the protein while the ligand
>         molecule was in protein pocket in original docked complex.
>
>         I hope it gives what I am trying to do, and where I am getting
>         stuck.
>
>         I am looking for some suggestions and more insight of the problem to
>         solve it.
>         Earlier I have done same procedure successfully for a different
>         docked
>         complex.
>
>
>     So you already have the coordinate file from which you wish to begin
>     MD, and all you need are topologies. One approach is to generate
>     your ligand .itp file with PRODRG as above, and your protein .top
>     file with pdb2gmx from the same coordinate file with the ligand
>     absent. Now you can simply take the protein.top file, #include the
>     ligand .itp file and amend the [ molecules ] section. This is now a
>     protein+ligand .top file.
>
>     Then you will need to take your original protein+ligand structure
>     file and perhaps modify the ligand part to conform with the atom and
>     residue names and ordering in the PRODRG output coordinate file -
>     but you don't need to concern yourself with the coordinates it produces.
>
>     As normal, you will need to take care that the coordinate file you
>     provide to grompp has the molecules ordered in the same order of the
>     [molecules] section, and that atoms within molecules have a
>     corresponding ordering in .top and coordinate file.
>
>     Mark
>     --
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