I agree with Vlad, I think that using PBSA for postprocessing makes sense
for systems like this. We recently developed a GB model for nucleic acids,
but this really is intended for MD where PB would be very slow. Since speed
isn't as important in your binding affinity calculation, you should
probably use a more accurate model than GB, especially for nucleic acids.
On Tue, Jun 23, 2015 at 7:32 AM, Vlad Cojocaru <
vlad.cojocaru.mpi-muenster.mpg.de> wrote:
> We had quite poor experiences with MMGBSA for protein-nucleic acids
> interactions not only because we got completely unrealistic absolute
> binding free energies but also because of rather poor agreement with
> experiment of relative dGs. Therefore, we use MMPBSA.
>
> For the protocol we use see the paper by Merino et al. in Structure 2014
> (Structural basis for the SOX dependent redistribution of OCT4 ...) .
> Although in the paper we focus mostly on DNA-mediated protein-protein
> interactions, we did play with the protocol to optimize as much as possible
> the protein-DNA energies.
>
> A word of caution: multiple tests with the PBSA parameters beyond those
> specified via MMPBSA.py is required.
>
> We are also preparing a follow up study with more discussion on the
> influence of the PBSA parameters on the results.
>
> Hope this helps
> Vlad
>
>
>
> On June 23, 2015 12:32:15 PM CEST, Muthukumaran R <kumaran.bicpu.edu.in>
> wrote:
> >Dear amber users,
> >I found from literature and mailing list that implicit simulations for
> >nucleic acids is not properly parameterized. I have done explicit
> >solvent
> >simulations for protein-DNA and protein-RNA complexes. I want to study
> >the
> >specificity of protien towards DNA/RNA, in this regard I have performed
> >binding energy calculations using mmgbsa (AMBER 12 and Amber tools 13)
> >
> >Input used:
> > &general
> > startframe=20000, endframe=25000,interval=50,
> > verbose=2, keep_files=1,
> > /
> > &gb
> > igb=5,
> >
> >Queries
> >
> >1. is it possible to study specificity using MM-GBSA.
> >2. As it is a relative method, is it meaningful to compare the binding
> >energies of DNA and RNA?
> >3. In regard to the gb model, I have adopted igb=5 (modified OBC model)
> >as
> >used in "A Computational Study of Nucleosomal DNA Flexibility by Jory
> >Z.
> >Ruscio and Alexey Onufriev". is this still an accepted model for
> >studying
> >nucleic acids.
> >
> >
> >Apart from MM-GBSA, is there any other analysis/method for studying the
> >specificity of Protein towards DNA and RNA.??
> >_______________________________________________
> >AMBER mailing list
> >AMBER.ambermd.org
> >http://lists.ambermd.org/mailman/listinfo/amber
>
> --
> Sent from my Android device with K-9 Mail. Please excuse my brevity.
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Received on Tue Jun 23 2015 - 05:00:03 PDT
