[gdkwiry53]

I have carried out some calculations based on an enzyme catalysed reaction, once using quantum mechanically modelled enzyme residue and once modelling it using molecular mechanics. I have found that the MM method gives a higher stabilisation energy for the transition state than when modelled quantum mechanically, could anyone tell me why this might be?

[Corribus]

I think more details are needed. What exactly are you modeling and what are the models? "Quantum mechanical model" is very vague, for example.

[Vrig]

What? Is your question why you get different answer from QM and MM calculations? Wouldn't this be expected almost all the time?

In QM calculations for instance the results you obtain will vary from method to method. It will vary with programmes, with basis sets and with coordinates.

[Irlanur]

of course you get different answers.
I wonder how you calculate a transition state energy in MM? how do you parametrize the interactions with a highly reactive Molecule? how do you model the protein in the QM? I don't think you calculate the whole enzyme+solute...
questions over questions to that question. in what position are you? what's the actual problem?

[gdkwiry53]

Sorry for being so vague! If i'm honest I don't completely understand the calculations involved but i'll try and explain as best I can:

The reaction involved is the enzyme catalysed intermolecular reaction of chorismate to prephenate. The basic idea was to use a QM/MM model of the enzyme in order to calculate the stabilisation energy associated with the enzyme. There were four different activation energies calculated:
-Enzyme catalysed reaction with MM Arg90
-Enzyme catalysed reaction with QM Arg90
-Gas-phase with MM Arg90
-Gas-phase with QM Arg90
These were then used to calculate the stabilisation energies. 

Basically it was found that when the Arg90 residue was modelled using MM, the stabilisation energy for the transition state was higher than when using QM.

I'm sorry if this is really vague, it wasn't explained very well, hence the confusion.
I understand that the values will obviously differ with different methods, but why would QM give a lower stabilisation energy?

[Irlanur]

The reaction involved is the enzyme catalysed intermolecular reaction of chorismate to prephenate

There is a very nice story behind this reaction. May I ask where you are working, just because I'm interested;)

concerning your question, I am afraid I still can't say anything. I assume you use some kind of Force-Field for the MM, which one do you use? I personally would assume that this approach just fails completely if you're looking at an Enzyme catalysed pericyclic reaction as a claisen rearrangement.

concerning QM: did you use DFT or some HF-related method? which Basis set? how did you model the protein? ...?

from my point of you, I would be very critical about both approaches, so I don't think you get an answer why the QM result is lower... why is this the question anyway? did you compare it with experiments?