In some threads a while ago, we had numerous discussions about doing
MMPBSA on protein-nucleic acids interactions ...I agree with Dave that
values of -250 kcal/mol (assuming the dG represents the binding
affinity) are very far away from the correct values to be reliable for
estimating ddGs ! Possibly, some of the problems lie in the protocol you
are using. In particular, the default values for a lots of parameters in
MMPBSA in Amber 15 or older are not suitable for protein-nucleic acids
interactions (I did not run yet MMPBSA with Amber 16) ....
In this paper (
http://www.ncbi.nlm.nih.gov/pubmed/25126959), we present
similar calculations for a protein-DNA complex with absolute values
(Table 3) that for some of the protocols we tried are much closer to the
experimental values. The values are very sensitive to a lots of
different input parameters.
Best wishes
Vlad
On 09/14/2016 03:49 PM, David A Case wrote:
> On Wed, Sep 14, 2016, hari krishna wrote:
>> We have carried microsecond simulations for a protein (800 aa) - RNA (17
>> bp) systems. Various modified RNA molecules have been used to find the
>> binding specificity/affinity with the same protein. The free energy of
>> binding was calculated using MM-PBSA method. The entropic contribution was
>> calculated using NMODE method. The free energy values (dG) are in the
>> range of -250 kcal/mol.
> It's not clear from your email what you mean by "dG": is this the estimated
> value for the protein-RNA association energy? If so, something is seriously
> amiss. If you are making errors of hundreds of kcal/mol in the aboslute
> binding affinities, it's hard to be sure that these errors will all cancel
> in the ddG calculations.
>
> I understand that many people in our field assume that there will be this sort
> of error cancelation, so that ddG values might be useful even where the
> underlying dG values are not. But I have never been at all happy with this
> idea: there is a fair likelihood that some really important feature (specific
> metal ion effects?) is missing from the model.
>
> .....dac
>
>
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>
--
Dr. Vlad Cojocaru
Computational Structural Biology Laboratory
Department of Cell and Developmental Biology
Max Planck Institute for Molecular Biomedicine
Röntgenstrasse 20, 48149 Münster, Germany
Tel: +49-251-70365-324; Fax: +49-251-70365-399
Email: vlad.cojocaru[at]mpi-muenster.mpg.de
http://www.mpi-muenster.mpg.de/43241/cojocaru
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Received on Wed Sep 14 2016 - 08:00:04 PDT
