in principle such comparisons can be done, but when you ask "is it correct"
there is not really a definitive answer because the different ways of
calculating binding affinities have many different assumptions and
approximations. If you have the "real" binding free energy of 2 proteins,
then yes you can compare them. What you need to ask next is whether the
approximations you have made to the "real" free energy makes this
comparison less accurate.
On Fri, Apr 1, 2016 at 12:49 AM, Sangita Kachhap <sangita.imtech.res.in>
wrote:
>
>
> Dear Carlos
>
> Thanks for the reply but I need to know that is it correct to compare
> the binding free energy of two protein of the same family but different
> in number of total residues as well as number of positively charged
> residue.
>
> With regards
>
> On 2016-03-28 2:36 pm, Carlos Simmerling wrote:
>
> > in principle, binding affinity is connected to free energy through the
> > usual transformation between free energy and equilibrium constant, where
> > delta G = -RTlnK. You do need to make sure to understand how the Kd was
> > measured, though, and often people are really measuring other quantities
> > such as Ki or even IC50. If you really know the equilibrium constant then
> > the conversion is straightforward. having said this, though, be aware
> that
> > in MM-PBSA you are normally not calculating the absolute binding
> affinity.
> > There are many approximations involved as well, especially or large
> > molecules such as proteins and DNA, and for highly charged interfaces
> like
> > these problems have, and the potential for involvement of structured
> water
> > or even ions. It does sound like your results are opposite of the
> expected
> > trend, but I don't find it surprising. I suggest doing some reading about
> > free energy calculations, there have been a number of good reviews
> lately,
> > and also some new methods for calculating absolute binding free energies
> > (it's rather costly compared to MM-PBSA though). For the system you're
> > studying, look for other published studies that successfully use MMPBSA
> to
> > calculate protein-DNA binding affinities. I expect it's very challenging.
> >
> > On Mon, Mar 28, 2016 at 2:55 PM, Sangita Kachhap <sangita.imtech.res.in>
> > wrote:
> >
> >> Dear All I am working on understsnding the mechanism of protein-DNA
> ternary complex formation. One protein has more banding affinity (kd value)
> to target DNA than second protein. When I was calculating the free energy
> of binding of indivisual protein to target DNA, protein having less
> affinity to target DNA showing more negative binding free energy than
> protein having more affinity but showing less negative binding free energy.
> I want to know that, is it correct way to relate kd value with MMPBSA
> calculated binding free energy?
> ---------------------------------------------- Sangita Kachhap Senior
> Research Fellow C/O Dr. Balvinder Singh Bioinformatics centre
> CSIR-Institute of Microbial Technology Chandigarh, Sector-39A, INDIA
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> --
>
> ----------------------------------------------
> Sangita Kachhap
> Senior Research Fellow
> C/O Dr. Balvinder Singh
> Bioinformatics centre
> CSIR-Institute of Microbial Technology
> Chandigarh, Sector-39A, INDIA
> ----------------------------------------------
>
>
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Received on Fri Apr 01 2016 - 07:30:03 PDT
