Hi,
Thank you very much for your reply. Most of your guess is right. The
ligand has a phosphoric group (PO4), and this PO4 is exposed to the
solvent.
If we want to consider the salt concentration, what's the range of
the salt concentration in PB and GB calculation should be reasonable
or acceptable.
Can we short the "cutoff" in MM calculation and PB or GB calculation,
such as from 999 to 25. (thus the GB or PB total may be negative)
Dose it make sense.
Best Regards
suxin
On Aug 18, 2006, at 10:50 AM, David A. Case wrote:
> On Wed, Aug 16, 2006, Suxin Zheng wrote:
>
>> I am doing mm_pbsa on high charged system as RNA with Amber8.0. While
>> some ligand also has negative charge (toward solvent) the PBTOT and
>> GBTOT will be positive as below. And the ligand with different
>> charges will give much more difference in PB and GB. It's hard to
>> compare different ligand's energy.
>> How to deal with such situation. I use the default parameters in
>> mm_pbsa.
>> # DELTA
>> # -----------------------
>> # MEAN STD
>> # =======================
>> ELE 4009.76 0.00
>> VDW -24.66 0.00
>> INT 0.12 0.00
>> GAS 3985.23 0.00
>> PBSUR -2.55 0.00
>> PBCAL -3914.80 0.00
>> PBSOL -3917.35 0.00
>> PBELE 94.96 0.00
>> PBTOT 67.88 0.00
>> GBSUR -3.67 0.00
>> GB -3941.00 0.00
>> GBSOL -3944.67 0.00
>> GBELE 68.76 0.00
>> GBTOT 40.56 0.00
>>
>
> It is hard to say much without more information. I gather(?) that
> the DELTA
> above refers to binding of a negatively charged ligand to an RNA,
> and that
> your concern is that the computed net free energy (not including
> entropy
> terms) is positive. I'm also guessing(?) that you think this is
> not wrong,
> perhaps because there is some experimental data that contradicts this.
>
> As you can see, I'm having to guess a lot about what the real
> problem is,
> especially since to also refer to "ligand with different charges".
> It is
> known that computing the absolute affinity of RNA for charged
> ligands by
> MM-PBSA is quite a difficult chore. See for example (for a
> positive ligand):
>
> %A V. Tsui
> %A D.A. Case
> %T Calculations of the Absolute Free Energies of Binding between
> RNA and Metal
> Ions Using Molecular Dynamics Simulations and Continuum Electrostatics
> %J J. Phys. Chem. B
> %V 105
> %P 11314-11325
> %D 2001
>
> On the other hand, neutral ligands seem to fare much better, e.g.:
>
> %A H. Gouda
> %A I.D. Kuntz
> %A D.A. Case
> %A P.A. Kollman
> %T Free energy calculations for theophylline binding to an RNA
> aptamer:
> %Comparison of MM-PBSA and thermodynamic integration methods.
> %%J Biopolymers
> %V 68
> %P 16-34
> %D 2003
>
> Maybe looking at these, or other similar calculations, will provide
> some
> insight. If you in fact have a negative ligand binding to RNA, you
> might also
> want to look at the (computed and experimental) salt-dependence.
>
> ...dac
>
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Received on Sun Aug 20 2006 - 06:07:20 PDT
