Dear Dr. Jason,
Just as your prediction, the binding pocket always has some conformation re-organization when some big ligand interacts with it. Here I mainly use MM/PBSA to make a complarison on the single mutation effect on my ligand. So I think it should work.
Thanks for your help again!
Best wishes,
Rilei Yu
--- 09年10月11日，周日, Jason Swails <jason.swails.gmail.com> 写道：
发件人: Jason Swails <jason.swails.gmail.com>
主题: Re: [AMBER] Energy-from-MM/PBSA-VS-experiment
收件人: "AMBER Mailing List" <amber.ambermd.org>
日期: 2009年10月11日,周日,下午10:54
Rilei,
Depending on your system, the entropy contribution certainly can be that
great. Also don't forget that by using MM-PBSA you are making the
assumption that the receptor protein explores exactly the same
conformational space in both the bound and apo states, since you are
extracting the receptor atomic coordinates from the bound complex
simulation. The same holds true for the ligand. This is obviously not
correct in general, so your limited conformational
sampling for both the free ligand and receptor will be limited by the
conformations that they can adopt in the complex, giving you an
incomplete map of their accessible phase space.
In light of these assumptions, your results are not surprising.
Perhaps the greatest application of this method lies within
calculating Delta- DeltaG's, whereby you compare the relative affinity
of two ligands to the same receptor. In this case, you make similar
erroneous assumptions about both systems which tend to cancel each
other to a large degree. Thus I would suggest running MM-PBSA on
another ligand with the same receptor (if you have done these
simulations) and compare the delta-deltaG to the experimental value.
You should get much better agreement.
Good luck!
All the best,
Jason
2009/10/11 Rilei Yu <yulaomao1983.yahoo.com.cn>
> Dear Amber users,
>
> After installing amber10 in my computer yesterday, today I have tried to
> use MM/PBSA to calculate the binding Energy for my complex. When I obtained
> the result I found it was -80 Kal/mol, that is really much larger than the
> experiment value. Based on the formula: Delta-G=-RTlnKd, I can obtained the
> experimental value is about -11Kal/mol (about 1-10 nM for KD). There is so
> much difference!
>
> I know here the dis-favorable entropy was neglected, but can entropy really
> introduce such big diffrence? What really makes me happy is that the total
> electrostaric energy is really similar with the value calculated using apbs,
> but using MM/pbsa can really improve the calculation efficiencey!
>
> I have made some revision based on my experience to use APBS, I do not know
> weather my revision is reasonbale or not. So I have attached it to this
> email, and hope people here can give me some suggestion.
>
> What is more, I also came across some bugs:
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> No skew or curtosis when zero variance in moment
> But these bugs above, may not influence me to calculate the energy.
>
> Here can anyone give me some suggestion?
>
> Thanks for your help!
>
> Regards,
>
> Rilei Yu
>
>
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--
---------------------------------------
Jason M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Graduate Student
352-392-4032
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Received on Sun Oct 11 2009 - 16:00:03 PDT
