Re: help in FEP calculations_binding free energy difference between 2 inhibitors

From: Chirag Vora (chirag740_at_gmail.com)
Date: Mon Sep 05 2011 - 16:36:04 CDT

Dear Bruno,
The way you presented "thermodynamic cycle" appears acceptable.

In your case PERTURBATION is disappearance of Re(CO)3. Such method is
adopted to predict absolute solvation energy.
See this JCTC article http://pubs.acs.org/doi/abs/10.1021/ct900587b

To have better correlation between experimental and FEP calculated values,
you must divide your perturbation into intermediate steps.
In other words state A (lambda=0) to state B (lambda=1) conversion can
be expressed through few intermediate steps. A ---> A1 --->A2 --->B and so
on.

>
> Please let me know if I got the termodynamic cycle correctly
>
>
> DeltaG1
> Ligand .... Re(CO)3 : enzyme ---------> Ligand .... Re(CO)3 +
> enzyme
> | DeltaG4
> | DeltaG2
> |
> |
>
> Ligand : enzyme --------> Ligand + enzyme
> DeltaG3
>
>
> DDbind = DeltaG1 - Delta3 = DeltaG4 - DeltaG2
>
>
> The way you presented "thermodynamic cycle" appears acceptable.

> I calculate the "transformation" of the Rhenium complex into the ligand
> in water (DeltaG2 = -31,93 Kcal/mol) and in the protein (DeltaG4 = -31,05
> Kcal/mol).
>
>
> DeltDeltG = DeltaG4 - DeltaG2 = - 0,886 Kcal/mol
>
>
> The obtained results are in good agreement with the experimental results--20cf307ca21681ed8f04ac387f6d--

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