[AMBER] Refitting charges with MCPB destabilizes the active site

From: Casalini Tommaso <tommaso.casalini.chem.ethz.ch>
Date: Wed, 29 Jul 2020 11:23:44 +0000

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,


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Received on Wed Jul 29 2020 - 04:30:02 PDT
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