[gmx-users] SMD pulling question

Justin A. Lemkul jalemkul at vt.edu
Sat May 15 17:46:09 CEST 2010

Hi Chris,

I think I've delved too far into speculation and I probably shouldn't have :) 
I'm not talking about applying any sort of restraint during the calculation of 
the PMF, that would certainly not be appropriate.  An umbrella potential for 
restraining the distance is all that's needed, restraining the relative COM 
distance and not the absolute COM position.

My concerns were for taking care of an SMD protocol that (in theory) could be 
conducted in such a way that caused problems in the system (all very 
hypothetical), i.e. hitting a moving target, if you will.  This shouldn't happen 
if care is taken to conduct the SMD properly.  I'll avoid tangents from now on :)


chris.neale at utoronto.ca wrote:
> Dear Justin:
> I still disagree. I know it's a fine point, but I think it's important.
> The PMF would, I presume, be created by applying a relative position 
> restraint along Z between the center of mass of a large ligand and the 
> center of mass of a bilayer and slowly changing the relative position to 
> which the distance is restrained.
> I don't see how an absolute restraint on the COM of the bilayer would 
> affect the stability -- or even the dG results -- in any way. Perhaps 
> you're talking about using weak position restraints in X,Y,Z on, say, 
> the lipid phosphates? The shape of the PMF would be all wrong, but I 
> suppose that there are cases where this might be a good idea.
> Chris.
>> I guess that I am missing something, but how would restraining the
>> position of the bilayer COM in absolute space have any affect on
>> anything at all? I certainly agree that one wants to observe if the
>> membrane has been destabilized, but if so then I think the solution
>> would be slower pulling and not an additional restraint on the COM of
>> the bilayer in absolute coordinates. Perhaps this is what you meant
>> Justin and I just got caught up in your word "unless".
> Indeed, by "unless" I am simply considering the case that some large 
> molecule is
> being forced against the membrane, causing it to somehow destabilize.  I 
> guess
> that's a bit of a far-fetched hypothetical, but in the absence of any 
> additional
> information about the goals of the SMD, it was more of a broad "just in 
> case"
> scenario.
> I certainly agree that the use of absolute restraints shouldn't be 
> necessary.
> -Justin


Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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