On Mon, 2014-03-17 at 07:58 -0700, Roza M wrote:
> My result for the binding free energy of Zif268-Dna complex was - 206
> kcal/mol
> and delta G value was -111kcal/mol, from this values I calculated kd
> and the result was very far from the experimental values.
MM/PBSA is notoriously bad for computing absolute binding free energies.
You can get decent estimates in some cases, but that requires careful
inclusion of solute entropy effects. (Look for citations from the Ryde
group regarding careful systematic studies of end-state free energy
methods like MM/PBSA).
> I made a pdb files from 1AAY.top and ( min.rst , heat.rst,
> density.rst, equil.rst, prod.rst) and viewed them in pymol to see
> where did I went wrong. I noticed that the zinc ion is moving away
> from its original position each step until finally it went out of the
> protein !!
> Although I used the following restraint each step
> Hold ZNA fixed
> 50.0
> RES 108 110
> END
> END
>
> How can I solve this problem?
Improved parameters, maybe you're missing some bonds... there are many
reasons you could be seeing problems like this. You should carefully
examine the parameters you used and compare them with the parameters
stored in the topology file (you can use ParmEd to do this with the
commands 'printBonds', 'printAngles', 'printDihedrals', etc.). This is
potentially a _very_ difficult problem to diagnose remotely via mailing
list. The key is to figure out exactly what is forcing the zinc out of
the protein -- is it an imaging artifact? electrostatic effects? is it a
result of restraints being put on the system? Designing a strategy to
fix a problem is made increasingly easier with the number of details you
know about the problem in the first place.
Good luck,
Jason
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Mon Mar 17 2014 - 09:30:02 PDT
