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

[abhigna polavarapu]

Thank you David I would certainly try this way.

On Mon, Feb 9, 2009 at 1:08 PM, David Mobley <dmobley at gmail.com> wrote:
> Hi,
>
>> 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.
>> abhigna
>
> The other thing I would remark in response to this is that you may
> want to think carefully about equilibration and convergence.
>
> Here's what I mean. There is in principle nothing wrong with
> drastically changing the electrostatics as long as your system is able
> to reach equilibrium again after you do this. Changing the
> electrostatics more slowly might have the same end result (or it might
> not).
>
> If  you don't believe your system will unfold in the absence of the
> copper ion, you can do what others suggested and apply some position
> restraints to the protein for  awhile to help it "equilibrate" in the
> absence of copper without unfolding. Or you can do what you suggest.
> If you want to do what you suggest I'd just make the B state charge on
> the copper ion be zero and use a small lambda step with the free
> energy code turned on using linear scaling. Then in a time-dependent
> way over the course of your simulation, turn the charge to zero. Once
> that's done, just delete the copper ion and proceed.
>
> However, at some point, you'll need to make sure you explore the
> energy landscape enough to establish some level of consequence that
> the preferred state for the protein in the absence of the copper isn't
> the unfolded state (I'm not talking experimentally, here -- I'm
> talking about with your particular parameters).
>
>
> David Mobley, Ph.D.
> Assistant Professor of Chemistry
> University of New Orleans
> New Orleans, LA 70148
> dlmobley at uno.edu
> Office 504-280-6445
> Fax 504-280-6860
>
>
>
>> On Tue, Feb 3, 2009 at 6:13 PM, David Mobley <dmobley at gmail.com> wrote:
>>> Perhaps this is obvious, but typically you only want to do free energy
>>> perturbation if you are interested in computing a free energy
>>> difference. If you are merely interested in structural properties of a
>>> different system (in this case, the protein without the copper there)
>>> you can simply make the change to the system (here, remove the copper
>>> atom) and run long enough for it to reach equilibrium.
>>>
>>> On Tue, Feb 3, 2009 at 3:55 PM, Polavarapu, Abhigna
>>> <polavara at indiana.edu> wrote:
>>>> Hi all,
>>>>        Thank you for the help till now and I successfully generated the forcefield Cu(I) binding protein. Now I wanted get the structure of non-copper bound form which I think I can do by perturbing the charge on Cu(I) and even perturbing the bonded and nonbonded parameters. Is there a way I can do this with Gromacs and when I read through chapter five I could understand the way it is done but I am not really confident about the protocol of getting the good structure for nonbonded protein with Cu(I). Can any one tell does this method works for this kind of situation where I have a Copper bound protein and by perturbing its bonded and nonbonding interactions one could arrive at the nonbonded protein structure and the energy difference. Thanks in advance.
>>>> abhigna
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