Re: [AMBER] TI calculation problem in pmemd

From: Hannes Loeffler <>
Date: Mon, 19 Dec 2016 07:48:53 +0000

On Mon, 19 Dec 2016 14:34:12 +0800
cuiyinglukitty <> wrote:

> Dear Amber users,
> I am trying to calculate the Thermodynamic Integration using soft
> core potentia ls in tutorial A9. The dG value in my calculation for
> A99V protein is -10.19 k cal/mol. However, the tutorial suggests
> that the alanine mutant is favoured ov er the valine mutant by about
> 10 kcal/mol. Should I also calculate the dG value for the complex,
> and then use the value = dGcom - dGprotein? If I want to calc ulate
> the sidechain mutations in a protein without any ligands, can I only
> use the dG value for the protein without performing any complex
> calculations?

The A9 tutorial demonstrates the calculation of the relative binding
free energy. In the first example the ligand is "mutated", in the
second it is a side chain of the protein. In either case there is an
underlying (closed) thermodynamic cycle so the free energy you get is
typically denoted as ddG. A single leg is physically not significant
and highly path dependent. E.g. the tutorial maps as many atoms as
possible in the side chain example but you could as well make the whole
side chain, for instance, into softcore atoms and you will get a
different dG (as mentioned in the tutorial).

So, you will need to answer yourself: free energy of what, and how to
design the thermodynamic cycle for that problem.


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Received on Mon Dec 19 2016 - 00:00:02 PST
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