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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Received on Mon Mar 28 2016 - 13:00:04 PDT
