Re: [AMBER] How do I study the dimerisation energy (i.e. energy required to form a dimer from two monomeric units) using AMBER?

From: David A Case <>
Date: Sat, 29 Aug 2015 07:38:01 -0400

On Sat, Aug 29, 2015, Suchetana Gupta wrote:

> My protein is a homodimer of some ~100 amino acids. I wish to calculate its
> energy required for dimerisation. The process that I am following is:
> 1. Take the dimer. Run 40ns MD. Calculate MMGBSA free energy.
> 2. Take a monomer. Run 40ns MD. Calculate MMGBSA free energy.
> Dimerisation energy=1-(2*2)

This sounds correct to me. Make sure that you are including an estimate of
the configurational entropy for both calculations.

> Now doing this, I am getting less dimerisation energy for a wild type
> protein than the drug resistant mutant one.

Do you know if this is right or wrong (i.e. compared to experiment)? If the
drug binds in the dimer interface, then your result would be consistent with
the mutant having drug resistance (since the binding pocket is less exposed
in the mutant than in the WT protein.)

> Moreover, the drug resistant variety (both monomer as well as dimer) is
> showing stabler energy value than WT counterpart.

You cannot compare (say) the free energy of the WT monomer with that of the
mutant monomer. They are not isomers of each other, and hence molecular
mechanics gives no information about their free energy difference.

A more accurate calculation (at least in principle) would be to use TI to
mutate the WT into the mutant sequence. Do this twice: once in the monomer,
and once in the dimer, and construct a thermodynamics cycle to generate
relative binding free energies.


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Received on Sat Aug 29 2015 - 05:00:05 PDT
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