Hi
1. I have tried to use free energy calculation but failed.
2. Is the procedure I listed in my last email reasonable ? (list as follows)
3. one protein + (10 ~ 20 ligand) will swell and have 2 to 3 times size of its orginal shape. That is known from
the experimental work => we want to knwo if the simulation can show this phenomena too.
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?
Thank you
Lin
Thank you
Lin
----- 原有信件 -----
寄件者: case <case.biomaps.rutgers.edu>
日期: 星期二, 2010 年 1 月 5日, 下午 9:11
主旨: Re: [AMBER] low concentration simulation ?
收件者: AMBER Mailing List <amber.ambermd.org>
> On Tue, Jan 05, 2010, Chih-Ying Lin wrote:
> >
> > 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)
>
> Can you say which protein and ligand you are dealing with. In the
> usual(English) meaning of these terms, a ligand would have a
> specific binding site
> to a protein, and one would not expect multiple ligands to be
> bound -- are you
> really dealing with extremely non-specific binding?
>
> > It will be a huge system to create a system with 20 mM and it
> will take
> > lot of simulation time.
>
> The usual approach to this problem is *not* to actually simulate a 20
> mM system, but rather to compute (estimate) the free energy of binding
> (using just one ligand and one protein), and then to use that free
> energyto compute binding probability at a given concentration. Is
> there some
> reason this approach will not work for you?
>
> ...dac
>
>
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Received on Tue Jan 05 2010 - 14:00:05 PST
