Hi Tommaso,
Sorry for the late reply. I am busy with preparing a class for this semester.
I think it makes sense that you got Ni ions leave the metal site quickly if you refit the charges using 3a or 3b option in MCPB.py, because it gives you charges for the bonded model, in which the charges of the Ni ions will be significantly less than their formal charges. I do not think change the level of theory for ESP fitting will help.
You said you want to calculate the ligand binding affinities, will the ligands bind to the metal ion(s) directly? If so, I would suggest you to use a nonbonded model (without fitting any charges) for the Ni ions. If the ligands do not bind to the metal site directly, you can use a bonded model instead.
Pengfei
> On Jul 29, 2020, at 7:23 AM, Casalini Tommaso <tommaso.casalini.chem.ethz.ch> wrote:
>
> Dear all,
>
> I am trying to simulate the Urease enzyme, which has an active site with 2 Ni ions.
>
> In order to perform this task, I am developing a non-bonded model using MCPB.py utility implemented in AmberTools (latest version).
>
>
> I refitted the charges of the ions and the residues involved in the binding, computing ESP at B3LYP/6-31G(d,p) level of theory, after a geometry optimization that involved only hydrogen atoms. I tried both 3a and 3b options.
>
>
> I am facing a problem: if I refit the charges, NI ions leave the binding site almost immediately. If I do not refit the charges, the binding site is stable for (at least) 100 ns at 310 K.
>
>
> I am not using a bonded model because I would like to test some ligands and I do not know whether it makes sense to use, e.g., MMPBSA to compute the binding free energy in this case.
>
>
> Have you experienced a similar issue? Can be useful to change the level of theory for ESP calculation?
>
>
> I thank you in advance for your support.
>
>
> With my best regards,
>
> Tommaso
>
>
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Received on Thu Sep 10 2020 - 13:30:02 PDT
