AMBER Archive (2007)

Subject: Re: AMBER: Abnormality in MM-PBSA result

From: Thomas Cheatham III (tec3_at_utah.edu)
Date: Fri Oct 19 2007 - 10:56:36 CDT

> I just want to know the reason of this abnormality. I have calculated the
> binding free energy of A-U (10 mers) and have got some abnormal results.
>
> One would typically expect to find an extremely favourable electrostatic energy
> and a dis-avourable solvation free energy. This symbolises the energy that ones
> has to use to de-solvate the binding particles and to align their binding
> interfaces.
>
> But in my case its opposite? why is it so? Is it normal? or is it becoz of some

I think you are confusing the energetics here and what each term means.
As nucleic acids are polyanions, there will be significant electrostatic
repulsion due to the phosphates and (in vacuo) this is unfavorable (hence
a large positive number). Similarly, a large polyion will be highly water
soluble and we would expect a large favorable electrostatic component due
to solvation (large negative number).

> ELE 4676.18 84.25
> PBCAL -4652.66 82.89

This is what you see. You also see that there is a balance between the
gas-phase electrostatics of the solute and the continuum electrostatics
solvation component of the electrostatics; these nearly cancel.

Finally, it is difficult to ascribe meaning to the absolute free energy
measured for a single conformation; what you really want to do is either
have some kind of free energy cycle (for example comparing duplex to free
single strands however how you treat the single strands is likely very
important) or compare relative free energies for different conformations
sampled.

-- tec3
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