Re: [AMBER] Questions about the TI methods in binding free energy calculations.

From: David A Case <>
Date: Mon, 2 Aug 2021 08:06:53 -0400

On Mon, Aug 02, 2021, wrote:

> I was confused by the thermodynamic intergration (TI)
> method for binding free energy calculation in this tutorial
> ( Does this
> method only use to compute the relative binding free energy?

Yes: the TI method is primarily useful for computing relative binding free
energies. It is possible to use TI to estimate absolute binding free
energies by converting a ligand into "nothing" (in both the protein and in
solution), but this requires some extra restraint steps as the ligand
becomes decoupled from its environment.

Tutorial 7.10 illustrates an alternative approach to absolute binding free
energy estimates, but this can be hard to use for ligands that are buried in
a binding pocket.

Others should chime in here about other tutorials or approaches for the
absolute binding free energy problem. This mailing list has seen a fair
number of recent posts about this issue.


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Received on Mon Aug 02 2021 - 05:30:03 PDT
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