On Mon, 2014-03-17 at 09:52 -0700, Roza M wrote:
> Dear Jason,
> First of all thanks a lot.
> I read that "It is known that zinc ion binding plays an important role
> in the stability and dynamics of the zinc finger proteins, which may
> affect the protein-DNA interactions.To maintain the tetrahedral
> structures of the
> zinc binding sites of the Cys2His2 coordination, the cationic
> pseudoatom representation42 was employed instead of a simple nonbonded
> representation. In the cationic pseudoatom representation, the zinc
> ion is replaced by a neutral zinc atom centered
> at a tetrahedron formed by four massless pseudoatoms with
> charge +0.5e. The +2e charge of the zinc ion is restored for
> the subsequent MM-PBSA analysis. The zinc ion coordination
> geometry obtained in this way was confirmed to be stable around
> 0.5 Å from the crystal structure throughout the MD simulations
> for all of the three zinc binding sites."
> From the following article:
> http://compbio.snu.ac.kr/publications/2010-zinc-finger.pdf
> Can this be the solution?
I have no experience simulating Zinc-containing systems. Zinc fingers
are pretty common, so I doubt this is the only paper reporting
simulations done with such systems. I would definitely encourage you to
experiment with strategies adopted by previous (successful) studies on
related systems.
> I did calculate the entropy
The normal mode and quasi-harmonic approximations used by the standard
MM/PBSA scripts in Amber are again fine for refining relative binding
energy calculations (generally), but I would not trust them for absolute
binding free energy calculations. Unless you carry out these end-state
free energy calculations following a very precise recipe (outlined by
the Ryde group), I would not expect trustworthy absolute binding free
energies from MM/PBSA.
HTH,
Jason
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Mon Mar 17 2014 - 10:30:02 PDT
