You are very unlikely to see the reaction happen 'spontaneously' (i.e.
without some way of forcing it to happen, such as Umbrella Sampling).
Consider the likely barrier to reaction (presumably in the range of 12-20
kcal/mole, but possibly higher for the level of theory you may use). Such a
barrier will almost certainly not be overcome in 300ps or even 300ns or
more of simulation, and if it does, I wouldn't trust it necessarily.
--Marc
On 29 June 2016 at 09:44, bharat gupta <bharat.85.monu.gmail.com> wrote:
> Dear Amber Users,
>
> Thank you again David for the advice on setting the initial system. I am
> able to run the QM/MM minimization now. But I have a few more questions
> about my study, which I have stated below.
>
> I am studying a simultaneous proton transfer, nucleophilic attack (by water
> molecule), bond breakage using QM/MM approach [in short single step
> inversion mechanism in Glycoside Hydrolase]. For this, I performed a
> classical MD simulation and selected the lowest energy structure for QM/MM
> calculation. Since I was not knowing which water molecule to consider for
> the reaction to take place, I, therefore selected the lowest energy
> structure and water molecules with in 3 Ang of the Acid residue, I included
> in the QM/MM calculation. My QM region includes 2 acid residues, 1 base and
> 3 water molecules. I want to know whether selecting starting structure in
> this manner for Q
> M/MM reaction (especially with regard to the choice of water molecule) is
> correct or not??
> My QM/MM protocol is as follows:
> 1. Minimization
> 2. Gradual heating with restraints of protein + ligand for 50 ps
> 3. Unrestrained NPT Equilibration 50 ps
> 4. Production run in NPT ensemble 300 ps.
>
> Do I expect to see the reaction taking place during the 4th step i.e.
> production run ? I have read that for the free energy profile for the
> reaction, I need to perform Umbrella Sampling, but I need to be sure
> whether I should first confirm whether the reaction is taking place during
> the production run or not? Am I going in the right direction?
> --
> *Best Regards*
> Bharat
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>
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Received on Wed Jun 29 2016 - 02:30:03 PDT
