Re: [AMBER] Physical chemistry question regarding entropy calculations in ligand-receptor system

From: David A Case <>
Date: Thu, 29 Jul 2021 07:59:46 -0400

On Wed, Jul 28, 2021, Liao wrote:

>We probably all know about the costliness of running entropy calculations
>in a large protein-ligand system. There were methods of pruning the protein
>and retaining the binding pocket region only to speed up the calculation
>reported in the years around 2012 or earlier. It works well since one only
>needs a delta S.
>Now I wonder, let’s say with a completely rigid receptor, if we want to
>compare the entropy difference of 2 poses of the same ligand, or entropy
>difference of 2 ligands, couldn’t we just remove the receptor completely
>and use the S value from the standalone ligands/poses only? Binding
>enthalpy can be calculated separately with the receptor present very
>quickly with MM/GBSA.

This won't work: the entropy term for the complex largely reflects how much
freedom the ligand has in its binding pocket. Two different poses would be
expected to have different amounts of "wiggle room", and hence different
entropy contributions. You would need to model both the ligand and the
receptor to make this work.


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Received on Thu Jul 29 2021 - 05:00:03 PDT
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