[CP2K:513] Re: Newbie Questions

[Jack Shultz]

Also for anything that is computationally expensive, I may run a serries of
estimates that generate samples. And then, perhaps analysis of the samples
will provide meaning.

On Jan 7, 2008 9:50 AM, Jack Shultz <jackyg... at gmail.com> wrote:

> Teo,
>
> I appreciate your comments and I am in the process of learning about
> molecular modeling. I am attempting to integrate these molecular modeling
> tools into my distributed computing project http://hydrogenathome.org
>
> I've hypothesized that it should be possible to identify catalysts based
> on structural data. Specifically I believe that it is possible to model
> transition state structures and their associated free energies and use that
> data with semi-empircal molecualr docking to model the transition state
> structures binding to reaction intermediates.
>
> I know that due to the induced fit model of enzymes, the active site of an
> enzyme goes through its own conformational changes to mold the substrate
> into a transition state structure. Maybe the active site in its native state
> is sufficiently close in structure to run a docking. Otherwise one would
> also have to run some kind of sampling on the different conformational
> changes in the protein structure.
>
> I understand that I need to start small. I will probably look at the most
> simple reaction with the most simple catalysts first. I may try a couple of
> modeling theories
> 1) Parameterized DFT
> 2) semi-empirical QM/MM.
>
> Perhaps treat it in a couple scenarios:
> 1) Run molecular docking on transition state structures with a catalysts
> where the TSS model is derived in a reaction isolated from any catalysts.
> 2) Then another scenario, run a molecular docking between the substrate
> and an enzyme. Generate a quantum box to of approximate 30 atoms and
> simulate a reaction within that area, ignoring external influences
>
> I don't know how realistic these ideas are, so really do appreciate having
> holes poked into it and an exchange of ideas. Thanks for your help.
>
> Jack
>
>
>
> On Jan 7, 2008 1:21 AM, Teodoro Laino <teodor... at gmail.com> wrote:
>
> >
> > Hi Jack,
> >
> > On 7 Jan 2008, at 03:12, jackyg... at gmail.com wrote:
> >
> > >
> > > I am looking at semi-empirical QM/MM as way to model catalyzed water
> > > splitting hydrogen generating reactions. I've been veting this idea
> > > among researchers and there seems to be problems with many of the
> > > molecular modeling techniques such as QMC and DFT as applied to my
> > > model.
> >
> > The information you are giving on the model are so few that i would say
> > semi-empirical can be even worst in treating water hydrogen bonds
> > compared
> > to DFT. Semi-empirical would be definitely faster but don't expect a
> > realistic
> > representation of the HB pattern for your system (few people here
> > have already
> > tried QMMM semi-empirical and can comment on that). Moreover the bond-
> > breaking
> > energies.. I would be surprised to see numbers in better agreement
> > than DFT.
> > Of course if you go for your own semi-empirical model, fully
> > reparametrized for
> > your system the situation can be different.. but that's another story..
> >
> > > Here is more specifically what I am proposing. I hope to run this
> > > analysis stochastically, perhaps treating the reaction in isolation,
> > > going through different energy pathways, generating a different
> > > transition state structures for each run along with associated free
> > > energy profiles. Using the results of these reaction models, I will
> > > run molecular docking analysis. So for a given reaction, we will have
> > > generated a great quantity of data. We can thus compare the
> > > theoretical vs the experimental, perhaps we can optimize these
> > > simulations with heuristic algorithms.
> >
> > Since I don't have more details on your project I can just give
> > general comments:
> > In principle it should work..  BUT.. consider that the reaction on a
> > smaller system
> > (what you call reaction in isolation) is mainly driven by the
> > potential energy (the entropic
> > contribution can be very small). If you go on a larger system the
> > entropic contribution
> > can be pretty large and you have no information on that since there
> > are no data you
> > can extrapolate from your small cluster and your conclusions "could
> > be" wrong.
> > So be careful in making your final conclusion in the logic chain
> > (models/extrapolations
> > from cluster to larger systems).
> >
> > > I have just started installing the cp2k. If it is posible to build
> > > this model with cp2k, I will really need help setting up these
> > > simulations. I have not given up on DFT yet.
> >
> > Which model?
> >
> > cheers,
> > Teo
> >
> > > >
> >
>
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