[gmx-users] Problem in preparation of the enzyme/substrate complex

[Mark Abraham]

Tsjerk Wassenaar wrote:
> Hi,
> 
> Even worse, this looks like a transition-state product. The hydrogen
> originating from the serine will not just have wandered off. It is
> unlikely that it happened to go sit on the other oxygen. Rather, the
> other oxygen, which would originally be double-bonded would probably
> form a strong hydrogen bond with some other residue (histidine?),
> rendering the carbon exposed enough for a nucleophilic attack by
> serine, followed by a series of events likely resulting in HO-R' being
> cut off. You won't be able to properly describe the transition state
> using classical means only.

Yep. Enzyme mechanisms are extremely difficult to model well, and very 
expensive if/when you get the QM-MM model right.

Mark