[gmx-users] Free energy perturbation of Cu(I) binding

Mark Abraham Mark.Abraham at anu.edu.au
Wed Feb 4 04:18:40 CET 2009

abhigna polavarapu wrote:
> Thanks David, But if I just remove the Copper atom and do the
> simulation as copper is charged there would be sudden change in
> electrostatics and the protein started unfolding when I ran the
> simulation for 10ns. So I thought perturbing the charge by little
> every time I can get a structure with more reasonable than artifacts.
> Can you please correct me if I am thinking in a wrong way.

No, you are on the right track, but I think you're trying to apply a 
tool that's not going to fix the underlying problem.

Metal-binding proteins that are expected to be stable with or without a 
bound metal are likely to undergo some kind of structural change as an 
inevitable consequence of the large change in the electrostatic 
environment. It is simply unreasonable to expect the same point MM 
charges to be adequate for modeling the structure and electrostatics in 
the two different states.

If, for some reason, you had sets of charges suitable for the two 
different states, then you simply need to do suitable equilibrations, 
possibly with position restraints initially, until the structures relax.

However it seems much more reasonable to be doing this with a QM/MM model.


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