[gmx-users] FEP energy errors with positional restraints?

Mark Abraham Mark.Abraham at anu.edu.au
Sun Feb 13 06:31:04 CET 2011

On 13/02/2011 3:57 PM, TJ Mustard wrote:
> On February 12, 2011 at 5:35 PM Mark Abraham <Mark.Abraham at anu.edu.au> 
> wrote:
>> On 13/02/2011 11:49 AM, TJ Mustard wrote:
>>> Hi all,
>>> I have been testing the ability of taking a sphere of a protein 
>>> around a ligand, and positionally restrain the specified alpha 
>>> carbons. I was hoping to keep non connected protein chains from 
>>> drifting apart. I have been able to run these md/fep jobs, but I get 
>>> huge interaction energies for the ligand, which has no positional 
>>> restraints on it. I also don't restrain any atoms within the rvdw, 
>>> rcoulomb and rlist radii. Am I thinking this is a possibility when 
>>> it is physically impossible to simulate?
>> I doubt it.
>>> Currently I am selecting all residues around the ligand that have an 
>>> atom within 20 Angstroms. I then save this as a pdb file and then 
>>> run it through pdb2gmx, manually create a posres.itp file for each 
>>> "chain" with their first and last residue's alpha carbon. Once I 
>>> turn off these positional restraints the FEP energies drop down to 
>>> "normal" levels.
>>> Does anyone have an idea what is happening?
>>> And if you do, can you please give a recommendation?
>> I'd guess you're not restraining how you think you are :-) Bear in 
>> mind that position restraints are indexed relative to a 
>> [moleculetype] (and must be #included there), and not the whole system. 
> First I tried setting this globally it the .top file with the 
> numbering corresponding to the atoms in question there, but found that 
> the .top file only runs the solvent molecules and all of my reference 
> atoms were outside the parameters (atoms 1-3 for water).

By default -DPOSRES will only restrain solvent because a) that's all 
it's meant to do, because b) that [position_restraints] block is local 
to the SOL [moleculetype], like I said.

> Then I setup the restraints argument in the Protein_chain_A.itp.itp 
> file to reference the posre_Protein_ends_chain_A.itp file I made.
> ; Include Position restraint file
> #include "posre_Protein_ends_chain_A.itp"
> #endif
> In the posre_Protein_ends_chain_A.itp file I entered the alpha-C atoms 
> (2 total both the first residue and last) for the protein.
> [ position_restraints ]
> ; atom  type      fx      fy      fz
>      5     1  1000  1000  1000
>    262     1  1000  1000  1000

Well, that should work, if you put this in the right [moleculetype] 
block. Whether that's enough of a restraint can't be said.

>> The combination of g_select and genrestr is probably a more reliable 
>> and documentable way to generate your position restraints.
> I tried using genrestr directly and found that the selection was 
> limited to the presets. I then tried to run a make_ndx to select the 
> residues that were the starting and terminating ends, but I don't know 
> how and if this program can do this task. I could manually find the 
> residue numbers and input them directly but knowing that I was looking 
> to restrain 6 atoms I decided to do it manually.

I thought you were trying to get all the alpha carbons outside a sphere, 
sorry. For just 6 atoms, sure do it by hand.
> I have yet to look at g_select, as I am just seeing if this idea would 
> work before I start making a automated script for this.

The point here is that it is straightforward to use g_select to "make an 
index group of alpha carbons further than a given distance from some 
location" and now you can use genrestr to make position restraints for 
that whole group.
> Would there be a better way to hold these atoms in the respective 
> locations. I could hold there distances constant.

Also possible, but (IIRC) the atoms have to be part of the same 
[moleculetype], which is awkward for inter-chain restraints. Either way, 
you have to address whether your restraints are perturbing the dynamics.

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