[gmx-users] Replacing a residue and continuing a simulation run

[Tsjerk Wassenaar]

Hi :)

I'd say that if the changes are small you should be able to get away
with it. You might want to start off the second part of the run with a
smaller time step to relax, though. If the change is from TRP to TRP*,
you only need to have a modified topology, without touching the
coordinates. You do need to set up a new  .tpr file from the the .trr
and the modified topology.

Hope it helps,

Tsjerk

On Tue, Mar 15, 2011 at 10:11 PM, Justin A. Lemkul <jalemkul at vt.edu> wrote:
>
>
> J. Nathan Scott wrote:
>>
>> Hello all,
>>
>> I was wondering, is it possible to replace a residue and then continue
>> a simulation using the new parameters/geometry of the new residue? The
>> reason I ask is that I am interested in performing simulations of
>> proteins with tryptophan in its excited state following a lengthy
>> equilibration with TRP in its ground state. I already have reliable
>> excited state atomic charges for the TRP atoms, and I suppose that I
>> will need to change at least some bonded terms to account for the
>> altered geometry of the excited state.
>>
>> I am still in the middle of reading the information that is out there
>> regarding parameterizing new molecules (since I'm using the CHARMM FF,
>> I've been starting to follow Alexander MacKerell's protocols), but I'm
>> still not quite sure as to how one would practically do this residue
>> replacement in the context of a Gromacs run. Will I need to manually
>> edit my .top file, or is there perhaps another way to update the
>> topology file with the new residue following the ground state
>> equilibration? How about coordinates, will I need to transform the TRP
>> coordinates to the excited state geometry by hand?
>>
>
> You would have to hack the topology.  Coordinates are another matter.  If
> you start making ad hoc changes, then what's the point of a continuation?
> Presumably, if you've designed the residue's topology correctly (including
> both bonded and nonbonded parameters), then the residue will adopt the
> correct geometry on its own.
>
> The complication comes with bonded interactions.  Are you using constraints?
>  If so, then changing bond lengths will cause the constraints to fail at
> step 0 (or very soon thereafter) and the simulation will crash.  You can get
> around this by setting "continuation = no" in the .mdp file, but again I
> wonder what the value of the continuation is.  You'd almost certainly have
> to forgo the use of .cpt files, supplying instead your .trr and .edr files
> to preserve as much of the previous ensemble as possible.  Even if you're
> not using constraints, the simulation may still fail if you're suddenly
> changing bond lengths, angles, etc by anything more than a very small
> amount.
>
>> Perhaps the most important question: is there a better way to do the
>> sort of residue replacement I'm contemplating, or is this something
>> that is just inherently going to be a bit messy?
>>
>
> I can't see any way around topology hacking.  If you need different
> parameters, you need a different topology.  It's going to be a bit messy,
> and I would encourage you to give some serious thought to the potential
> pitfalls I listed above.
>
> -Justin
>
>> Thanks very much for any insight or guidance you can offer!
>>
>
> --
> ========================================
>
> Justin A. Lemkul
> Ph.D. Candidate
> ICTAS Doctoral Scholar
> MILES-IGERT Trainee
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul[at]vt.edu | (540) 231-9080
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>
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-- 
Tsjerk A. Wassenaar, Ph.D.

post-doctoral researcher
Molecular Dynamics Group
* Groningen Institute for Biomolecular Research and Biotechnology
* Zernike Institute for Advanced Materials
University of Groningen
The Netherlands