[gmx-users] two question about calculating the binding free energy using g_lie method

[Michael Brunsteiner]

> Dear all
> Now i am trying to calculate the binding free energy of protein and ligand, I
> prefer to use the g_lie method as my system is very big and calculating the
> free energy by 'slow glow' or "perturbation" is a rather rough task,is that
> so?;)

the difference in the time effort when you compare a simple MD
to full TI or perturbation is (roughly) between a factor 10 and 100 

> Following is my two quesiton about g-lie.
>
> No1:
> When calculated the energy of interaction, i found that the Coul-SR
> (ligand--ligand) has a difference of about 30kJ/mol between free in water and

> binding with protein. i think this difference may due to change of 
> conformation
> of ligand.Is the g_lie method still suited when the conformatin change of
> ligand is rather large when it binding with protein?

I would guess it is not ...

> No2:
> for the ligand in my system has +1 charge, the PME and Cutoff method was
> respectively used  to calculate the Coul interaction. however, the difference
> of the result is huge:
> PME:Coul-SR(rcoulomb=0.9):          -278.337kj/mol
> PME:Coul-SR(rcoulomb=1.2):          -303.292kj/mol
> Cutoff:Coul-SR(rcoulomb=1.2):       -509.506kj/mol    
> gromacs 3.1.4(sigle)
> Is that reasonable .

you did not consider the longrange contribution to your
interaction energies obtained with PME (mind you, the short range
contribution to the electrostatic interactions obtained with PME or cutoff
are NOT supposed to be the same, even if you use the same cutoff)

calculating the long range contribution to these interaction energies
is possible but a bit cumbersome (it has been discussed in this list
several times) ... however, as far as I know LIE has originally been
developed with cutoffs (and un-charged ligands/receptors) I doubt its
applicability in such a case ...

good luck!
michael


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