I think usually one would use the method your talking about to develop a
better binder, which could lead to better activity. But yes, I would think
that once it's bound, your not getting any information about how well it
will lower the activation energy.
I'm not sure about modelling the transition state. In general for
generating parameters for something there are two parts, the first is
getting the partial charges and the second is assigning atom types based on
a forcefield. I would think you could use the normal methods to get the
partial charges if you had a structure of what you think the transition
state looked like, but I'm doubtful that any parameters exist to cover some
of the odd bonding patterns one might see in a transition state.
~Aron
On Sat, Dec 15, 2012 at 4:21 PM, Chris Chris <alpharecept.yahoo.com> wrote:
> I am trying to model the active site of an enzyme with a catalytic triad.
> Any catalyst will bind the substrate transition state more tightly than the
> substrate itself, correct? I am using Autodoc Vina and Amber/MMPBSA to
> assess the binding values of various substrates to an active site of an
> enzyme that contains a catalytic triad. As I'm doing this, I'm wondering
> what the docking and dG energy values really mean- afterall, I'm performing
> these simulations with a subtrate/ intermediate in their stable states- Not
> their transition states. Thus, why would I have any reason to believe that
> my substrates will bind in the correct geometry with respect to the
> catalytic triad? Only the transition state would bind in such a way-
> correct?
>
> Are we assuming that the substrate and the transition state are very close
> structurally? I think that would sometimes be the case but my knowledge is
> limited.
> Is there any way to generate a proposed transition state with some
> available modeling program?
>
> Is there a flaw in my thinking here? Thanks for any input
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>
--
Aron Broom M.Sc
PhD Student
Department of Chemistry
University of Waterloo
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Received on Sat Dec 15 2012 - 14:30:02 PST
