[AMBER] Query on thermodynamic integration of complexes involving metal ions

From: Muthukumaran Rajagopalan <kumaran.bicpu.edu.in>
Date: Wed, 31 Jan 2018 17:54:55 +0530

Dear AMBER users,

I am performing thermodynamic integration for the disappearing of few ions in protein complex.
I am using Sander to convert an ion (initial state) to a dummy atom (final state).
Initially, I create a lib file for the initial state. Then change the atom name of the ion to DN (Dummy atom) and charge to 0 in the .lib file to use as final state. I also load an .frcmod file to define the DN atom type with 0 non-bonded parameters.
I am modifying both the charge and vdw parameters at the same time to make the ion disappear.

I am following the tutorial in the below link as a starting point.

Since an ion disappears in the perturbed state, I am also using klambda=4.
I have tried with 3 clambda points as well as 9 points using the lambda and weight values given in amber tutorial.
As an example, I have shown the dv/dl averages for both 3 point and 9 point simulations.

charge+vdw; 3-point integral

deltaG of ligand in water

deltaG of complex in water


charge + vdW perturbation 9 point integral

deltaG of ligand in water

deltaG of complex in water


deltaG of ligand in water (klambda 4) 

deltaG of complex in water (klambda 4) with restraints


The use of klambda=4 makes a huge difference in the obtained deltadeltaG.
When I check the elec and vdw energies, the elec energies contribute almost entirely to the dv/dl (ex. dv/dl=470.0083; elec=488.4165; vdw=-18.4082).
This is understandable because, the ion-protein interaction is majorly electrostatic. 

Also, even with a restraint weight of 10, the ions move from their initial positions and so the energies may not be reliable.

How do I decide the number of clambdas required for my system. My system is relatively small (~700 atoms) and highly charged (~-20).
How do I handle the ion movement. Position restraints doesnt seem to work.

Any suggestions and pointers regarding this would be very helpful.

Thanks in advance.


R. Muthukumaran
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Received on Wed Jan 31 2018 - 04:30:02 PST
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