On Wed, Sep 07, 2016, Smriti Sharma wrote:
>
> I am trying to compute binding energy of ligand covalently bound in hexa
> coordinated heme protein. (Fe attached to 4 porphyrin N, 1 bonded with
> proximal His and 1 with ligand).
You cannot do this with molecular mechanics, which does not understand the
thermodynamics of covalent bond formation.
You could think about estimating the *difference* in binding energy between
a model heme compound, and the corresponding proteing complex. There is a
very old paper that attempted this:
%A M.A. Lopez
%A P.A. Kollman
%T Application of molecular dynamics and free energy perturbation methods to
metalloprotein-ligand systems II: CO and dioxygen binding to myoglobin
%J Protein Sci.
%V 2
%P 1975-1986
%D 1993
This assumes that the intrisic bond energy between iron and CO is unchanged
when the protein is present, adding strain to the iron-porphyrin system.
I'm not convinced that this is a good assumption, since the geometry of CO
binding changes (going from linear to bent).
There may be more recent papers on this subject: be sure to do a thorough
literature search.
It is possible to use mm/pbsa to look at this, although you would probably
want to do it "by hand" first.
...regards...dac
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Received on Wed Sep 07 2016 - 05:00:03 PDT
