Re: [AMBER] How to assess mutant-induced instability with MM-GBSA

From: David A Case <>
Date: Sat, 20 Mar 2021 09:08:07 -0400

On Fri, Mar 19, 2021, Matthew Guberman-Pfeffer wrote:
>To quantify the change in stability with MM-GBSA, would you run two
>separate calculations, each time only specifying the topology and
>trajectory for the complex (wild type or mutated system), and then take the
>difference in the reported free energies?

Here you would have two independent trajectories to analyze, one for
wild-type and one for mutant. The positive thing is that many errors and
uncertainties in the MM-GBSA model might cancel in comparing the two
results, since the systems are very similar. The downside is that the two
trajectories are indepedent: some conformational change might have taken
place in one system but not in the other.

Be sure you understand exactly what you mean by the term "change in
stability": are you defining with respect to a temperature-unfolded state?
with respect to a denaturant-unfolded state? something else? You always
need to think about both end states in doing a thermodynamic comparison.

Try to find papers that describe calculations similar to those you want to
do. See what choices were made, (you don't have to necessarily follow them,
but such knowledge always helps), and what sort of results were obtained.

....good luck....dac

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Received on Sat Mar 20 2021 - 06:30:02 PDT
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