QM/MM tutorial


QM/MM calculations on a Diels-Alder antibody catalyst.


III. Optimization of product, reactant and transition state geometries in water, using Linear Transit in gromacs

Introduction

We are now going to see how reaction barrier changes when we solve the reactants in water. Since water is a polar solvent we can anticipate that there will be an effect of some sort. In this part we first create and equilibrate a simulation box with the reactants and water molecules. Then we perform a Linear Transit calculation, using the reaction coordinate of the previous step (figure 3).

QM/MM subdivision

The system consists of the two reactant molecules solvated in water and one Na+ ion. The ion compensates the overall charge of -1 on the aliphatc tail (-R, figure 1)). This system is way too big to be treated at the QM level. Therefore we divide the system in a small QM part and a much bigger MM part. The QM part consists of the reactants, without the aliphatic tail and is described again at the semi-empirical PM3 level, while the remainder is modelled with the GROMOS96 forcefield. Figure 6 shows the subdivision used in this part of the tutorial.

Figure 6. Division of the system in a QM subsystem and an MM subsystem. The QM subsystem is described at the semi-empirical QM level,
while the remainder of the system, consisting of the reactants' aliphatic tail, the water molecules and the Na+ ion, is modeled with the GROMOS96
forcefield.

In this part of the tutorial we are going to perform again a Linear Transit calculation, but this time, the reactants are fully solvated. The details on how to perform a QM/MM Linear transit calculations in gromacs were discussed previously.

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Finding product, reactant and transition state geometries in water, using Linear Transit

The starting structure for this calculation is the transition-state analogue form the x-ray model, we have modified in the previous part of this tutorial. Then we place this structure in the center of a periodic box and fill that box with 2601 SPC water molecules and 1 Na+ ion. The total system is equilibrated, before the Linear transit computation is performed. As before we will skip this tedious procedure, which has nothing to do with QM/MM, and use the results instead (confin.gro). The steps we took in the equilibration process are described here.

We will again make use of scripts to perform the Linear Transit.

The create_tops.scr and the run.scr script are identical to the ones we used before, but the get_energies.scr script is slightly different. In vacuum we could simple take the total potential energy. In the water, and later in the protein, we don't want to know the potential energy of the complete system, but rather the internal energy of the reactans plus the contributions from the interaction of the reactants with the surroundings. So what we want is E(reactants)+E(reactant-solvent)+E(reactants-NA+).

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Conclusions

We have now found the geometries and energies of the transition state, the reactant state and the prodcut state of the Diels-Alder cycloaddition in water. Table 3 lists the QM/MM energies of these geomtries.

Table 3. Energies of the reactant,
transition state and product geom-
etries in water at the
PM3/GROMOS96 QM/MM level.
The last column lists the energy
differences with respect to the
reactant state.

E (kJ/mol)ΔE (kJ/mol)
Reactant-1202.40.0
Trans. St.-1062.9139.5
Product-1271.7-69.3

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updated 07/09/04