[gmx-users] a question about g_lie

[David]

On Sat, 2004-02-07 at 19:30, Jerry Song wrote:
> Hello, Dear gmx-users,
> 
>  
> 
> I have a question about g_lie.  I embedded a membrane protein-ligand
> complex in the lipid bilayer and performed the usual MD simulation. 
> I wish that I could use the resulting energy file to estimate the
> ligand binding affinity.  So the "solvents" here include the water,
> lipid bilayer and ion.  Then how can I calculate the Elj and Eqq at
> its unbound state?  
> 
>  
> 
> Can someone help me to clarify the procedure to calculate the linear
> interaction energy?   
> 
> Is the following steps right?
> 
>  
> 
> Perform the usual MD simulation the solvated protein-ligand complex 
> 
> Perform another MD simulation for free ligand and water. (If so, are
> there any specific requirements for the solvent system here? Do they
> have to be the same as the "solvent" system in the above step?) 

It depends! Is your ligand very hydrophobic (e.g. a quinole) then you
should consider using the ligand in the membrane as the reference system
(i.e. the solvent is the membrane).

> 
> Calculate the average value of LJ and Coulomb interaction energies
> between free ligand and water as the input for Elj and Eqq
Yes that's all simple and correct if you have saved the interaction
energy components. If you have used PME you need to do additional
simulations, check the archives.

Note that LIE calculations are useful mainly if you want to compare many
different ligands in the same binding pocket, since you have to
parametrize the factor for the Elj, in particular if your ligand is very
hydrophobic.

>  
> 
> Thanks a lot!   
> 
>  
> 
> Jerry Song
> 
> Department of Chemistry
> 
> Rensselaer Polytechnic Institute
-- 
David.
________________________________________________________________________
David van der Spoel, PhD, Assist. Prof., Molecular Biophysics group,
Dept. of Cell and Molecular Biology, Uppsala University.
Husargatan 3, Box 596,  	75124 Uppsala, Sweden
phone:	46 18 471 4205		fax: 46 18 511 755
spoel at xray.bmc.uu.se	spoel at gromacs.org   http://xray.bmc.uu.se/~spoel
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