[gmx-users] low concentration simulation ?

[Justin A. Lemkul]

Chih-Ying Lin wrote:
>  
> Hi
>  From Justin,
> "If you say that you have 20 mM
> of ligand, which corresponds to 18 ligands attached to one protein, why 
> not just
> put 18 molecules in your unit cell with one protein?  "
>  
> => I want to save the simulaiton time since i will run the simulation up 
> to 1 micro-sencond.
> => 18 ligand + one protein ( 7nm  x  7nm   x   7nm)
> => 10 ligand + one protein ( 6nm  x  6 nm  x   6nm)
> => ( 7nm  x  7nm   x   7nm)  is twice size of  ( 6nm  x  6nm   x   6nm)
> => increase four times simulation time
>  

Well, it's not quite twice the size, but I can see your motivation.  Every 
simulation is a balance between speed and accuracy (force field assumptions, 
cutoffs, etc).  To me, sequential addition of multiple components, especially 
after stripping out water and perturbing the equilibrium, is flawed.

Also realize that there are box shapes (dodecahedron and octahedron) that are 
far better than cubes that will save you a lot of water molecules.

>  
>  From Justin,
> "can you guarantee that the ligands will interact the same way as if
> you add ten at a time?  Will they aggregate?  Will they inherently bind the
> protein in the same way, or will it be different? "
> => I don't know, but I assume that will make little difference.
>  

Assumptions can be good or bad.  Be careful what you assume.  Consider this: if 
a reviewer asks this same question when you are trying to publish a paper, do 
you think he or she will be satisfied if you respond "we assume it will be fine, 
but we don't really know."

-Justin

>  
> Thank you
> Lin
>  
>  
>  
>  
>  
>  
>  
> Chih-Ying Lin wrote:
>  >
>  > HI
>  > I am simulating the protein + ligand + water molecules system.
>  > In the experimental work, the concentration of ligand is pretty low, say
>  > under 20 mM   (avearge 18 ligands attached on one protein)
>  > It will be a huge system to create a system with 20 mM and it will 
> take lot
>  > of simulation time.
>  > Instead, I create a 6nm x 6nm x 6nm simulation box and put one protein
>  > molecule with 10 ligands.
>  > After 100 nano seconds, 10 ligands are attached on the protein.
>  >
>  > Then, for this one protein with 10 ligands attached  + water molecules
>  > I will do the following steps =>
>  > 1. remove the water molecules
>  > 2. center the protein with 10 ligands attached in the 6nm x 6nm x 6nm
>  > simulation box
>  > 3. put another 10 ligands around the protein with 10 ligand attached
>  > 4. solvate the system
>  > 5. add ions
>  >
>  > Are the above steps make sense to create a low concentration simulation?
> Your procedure sounds more like a titration with increasing concentration,
> rather than modeling a low concentration system.  If you say that you 
> have 20 mM
> of ligand, which corresponds to 18 ligands attached to one protein, why 
> not just
> put 18 molecules in your unit cell with one protein?  You may never be 
> able to
> achieve the actual concentration, but you can certainly model the mole 
> ratio.
> The other concern would be - if a system initially had 20 ligands (or 18,
> whatever), can you guarantee that the ligands will interact the same way 
> as if
> you add ten at a time?  Will they aggregate?  Will they inherently bind the
> protein in the same way, or will it be different?
> -Justin
>  > Thank you
>  > Lin
>  >
> 

-- 
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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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